Genetics Research
rs717620
Gene: ABCC2 — ATP Binding Cassette Subfamily C Member 2
Chr 10:99782821
10q24.2
Non Coding Transcript Variant
Population Frequencies12
African
C 0.93531T 0.06469CC 0.874958CT/TC 0.120708TT 0.004334pop=65,530
African American
C 0.93419T 0.06581CC 0.872799CT/TC 0.122775TT 0.004425pop=63,270
African Others
C 0.9668T 0.0332CC 0.935398CT/TC 0.062832TT 0.00177pop=2,260
Asian
C 0.79414T 0.20586CC 0.630267CT/TC 0.327745TT 0.041988pop=13,480
East Asian
C 0.78858T 0.21142CC 0.620313CT/TC 0.336537TT 0.043151pop=10,614
European
C 0.801662T 0.198338CC 0.642993CT/TC 0.317336TT 0.03967pop=548,270
Latin American 1
C 0.84778T 0.15222CC 0.722036CT/TC 0.251491TT 0.026473pop=10,728
Latin American 2
C 0.85781T 0.14219CC 0.735865CT/TC 0.243891TT 0.020244pop=16,696
Other
C 0.83216T 0.16784CC 0.696873CT/TC 0.270574TT 0.032553pop=21,872
Other Asian
C 0.8147T 0.1853CC 0.667132CT/TC 0.295185TT 0.037683pop=2,866
South Asian
C 0.8924T 0.1076CC 0.797225CT/TC 0.190289TT 0.012486pop=8,650
Studies576
Unread Studies576 ▼
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Genetic and clinical predictors of voriconazole pharmacokinetics and hepatotoxicity: focused on CYP2C19 normal and intermediate metabolizers
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Multi-Omics in Predicting Lamotrigine Neurotoxicity: Current Opportunities
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Previous research has shown, that ABC transporters gene expression level can predict the efficacy of therapy. However, other mechanisms of gene activity are rarely …
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… Así mismo, los portadores del alelo de riesgo rs717620-T, similar a los haplotipos de riesgo … de que la variabilidad en rs1885301 y rs717620 modula la toxicocinética del mercurio y, por …
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… Notably, the associations involving rs7439366, rs7311358, and rs717620 are consistent with prior evidence, reinforcing their potential relevance in MPA pharmacogenomics. Integrating …
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… A total of seven studies were conducted on the association between the ABCC2 rs717620 genotype and toxicity. Three of these studies demonstrated a correlation between the TC or …
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… Meanwhile, carriers of the T allele in ABCC2 (rs717620) had a higher risk of hematological side effects. The second very recent study applied WES to investigate genetic factors …
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Sinusoidal obstruction syndrome (SOS) is a known adverse effect of oxaliplatin, causing significant morbidity and cessation of chemotherapy. Recent studies suggest single nucleotide …
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… rs717620), were associated with delayed MTX clearance. Patients carrying the variant allele of ABCC2 rs717620 … in MTX elimination associated with ABCC2 rs717620, the study did not …
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… rs717620), were associated with delayed MTX clearance. Patients carrying the variant allele of ABCC2 rs717620 … in MTX elimination associated with ABCC2 rs717620, the study did not …
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… Notably, the associations involving rs7439366, rs7311358, and rs717620 are consistent with prior evidence, reinforcing their potential relevance in MPA pharmacogenomics. Integrating …
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… Notably, the associations involving rs7439366, rs7311358, and rs717620 are consistent with prior evidence, reinforcing their potential relevance in MPA pharmacogenomics. Integrating …
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Statin‐induced myotoxicity (SIM) is a common adverse effect of simvastatin therapy, which can negatively impact patient adherence and treatment outcomes. This study aims to …
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Objective Genetic variations in the ABCC2 gene have been proposed to influence resistance to antiseizure medications, but published findings to date are inconsistent. We aimed to …
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The combination of thiopurine and methotrexate (MTX) is a standard co-therapy regimen for acute lymphoblastic leukemia (ALL). Despite its efficacy, this regimen is constrained by a narrow therapeutic window and considerable inter-individual variability, which heightens the risk of drug-induced liver injury (DILI). MTX-induced metabolic strain further destabilizes cytokine-sensitive thiopurine detoxification pathways during systemic inflammation. Conventional pharmacogenetic (PGx) testing for TPMT and NUDT15 variants is effective in predicting myelosuppression, but often fails to detect hepatotoxicity as an adverse effect, suggesting a clinically significant genotype-phenotype difference. This review examines the molecular determinants of DILI, emphasizing the role of secondary metabolic pathways and transporter dynamics as key modulators of risk. The study describes cytokine-mediated (IL-6, TNF-α) transcriptional suppression of cytochrome P450 enzymes and hepatic transporters (SLCO1B1, ABCC2/4) not merely as secondary modulators, but as the primary determinants of localized, tissue-specific drug exposure through disrupted nuclear receptor signaling (PXR, CAR, HNF4α). This mechanism promotes functional phenoconversion and toxic molecular shunting, leading to increased intrahepatic drug exposure. It synthesizes the current knowledge on the metabolism of thiopurine and MTX, focusing on the genetic and non-genetic factors influencing toxicity and their interactions. The review also critically evaluates the limitations of static PGx-guided dosing. It highlights the need for comprehensive, real-time risk assessment that integrates gene-environment interactions, multi-omics data, and clinical monitoring to improve precision therapy for ALL. This approach combines extended PGx profiling, transcriptomic monitoring, and clinical biomarker assessment to provide a transformative strategy for precision drug delivery.
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… 24C > T (rs717620) variant was significantly associated with all-grade neutropenia in the second cycle. The ABCC2 c.-24T variant has been associated with lower mRNA levels, …
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… In addition, polymorphisms of the aforementioned genes are also predictors of chemotherapy toxicity, such as rs1045642 in the ABCB1 gene associated with neutropenia or rs717620 …
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The main objective of this study is to investigate whether the CYP3A4/5 and ABC transporter genetic polymorphisms could affect the pharmacokinetics (PK) of rivaroxaban in Chinese …
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HMG-CoA reductase inhibitors, commonly known as statins, are among the most widely prescribed and extensively studied drugs used in managing cardiovascular conditions by …
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Demographics and kidney function contribute to variability in lamivudine and tenofovir drug concentrations. The aim was to assess, for the first time, the pharmacokinetic variability …
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… greater in patients with the CT genotype for the rs717620 ABCC2 variation than in those … However, a small number of patients with homozygous genotypes for rs3740066 or rs717620 …
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Although the role of pharmacogenomics (PGx) in personalized pharmacotherapy has been well established, its implementation in clinical practice lags behind. In this article, we present …
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This literature review provides examples of the influence of certain genetic variants on health outcomes after dietary polyphenol consumption or supplementation…
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Previous genetic studies on the genetic makeup of Arab populations highlight the diversity resulting from the distribution of specific genetic markers among various Arab descendant …
25
Cancer pharmacogenetics has become a cornerstone of precision oncology. It offers the potential to optimize therapeutic outcomes by tailoring treatments to individual genetic profiles. …
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Pharmacogenetic Implications in the Clinical Approach to Antiretroviral Therapy. a Systematic Review
Medicine Based on the PharmacoGenomics (MBPG) of antiretroviral agents against HIV is undergoing key advances in recent years, which can optimize the efficacy and …
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Pharmacogenetic variability has been reported to influence the efficacy and safety of immunosuppressive therapies in early stages of kidney transplantation. This study …
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… Polimorfisme rs717620 dan rs3740066 dilaporkan memiliki asosiasi paling konsisten, terutama pada populasi Asia. Varian ini memengaruhi tingkat ekspresi dan efisiensi transporter, …
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Epilepsy is a devastating neurological disorder mainly associated with impaired synchronic discharge that leads to sensory, motor, and psychomotor impairments. Till now, about 30 anti…
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Next-Generation Sequencing (NGS) methods specifically Whole-Exome Sequencing (WES) have demonstrated promising findings with a high accuracy of 91%-99% in …
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… -treated oesophageal cancer, significant correlations were observed between ABCC2 rs12762549 and ABCB1 rs1045642 with severe neutropenia (71), and ABCC2 rs717620 with …
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Modern therapeutic approaches to non-Hodgkin’s lymphomas (NHL) in children consider the tumor morpho-immunohistochemical features, stage and prognostic risk group…
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Rheumatoid arthritis (RA) is a chronic inflammatory disease that can be managed with a range of therapeutic treatments. Methotrexate (MTX) is a first-line treatment for RA; however, its …
34
Colorectal cancer is the second most prevalent cancer in Chile, affecting both sexes. Late-stage diagnosis occurs in approximately 25% of cases, with a five-year survival …
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… The rs717620 SNP in the ABCC2 gene has been discussed in four articles [22,31,32,35] … The ABCC2 gene encodes ATP-binding cassette subfamily C member 2 and the rs717620 …
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Deferasirox is a widely used oral iron chelator in patients with transfusion‐dependent thalassemia, but considerable variability in treatment response remains a clinical challenge. This …
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… , and rs717620 prominently corresponded to a good and moderate response as per the EULAR criteria. SNPs in the transporters ABCC2 rs3740066 and rs717620 were prominently …
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High-dose methotrexate (HD-MTX) is essential in treating acute lymphoblastic leukemia (ALL), but its pharmacokinetics and toxicity are influenced by transporter and …
39
Colorectal cancer is one of the most prevalent cancers worldwide. We have thus focused on studies on the association of genetic polymorphisms with treatment response and adverse …
40
… However, they observed a positive association with the risk of ASM resistance in the combined and Asian populations for both rs717620 and rs3740066, particularly under the recessive …
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Valproic acid (VPA) has great individual differences in clinical efficacy, the study aimed to investigate the effects of VPA-related pharmacogenomics on its antiepileptic efficacy, providing …
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Simvastatin, an HMG‐CoA reductase inhibitor, is widely used for hypercholesterolemia but may cause myotoxicity linked to its plasma concentration. Pharmacokinetic gene …
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Background Drug-resistant tuberculosis (DR-TB) is associated with alterations in drug pharmacokinetics (PK), aberrant expression of efflux pump transporters, and genetic mutations. …
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… subfamily B member 1 (ABCB1) rs1128503, ATP-binding cassette, subfamily C, member 1 (ABCC1) rs246240, ATP-binding cassette, subfamily C, member 2 (ABCC2) rs717620, solute …
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… 结论CYP2C19,CYP2C9 rs1057910,CYP3A5 rs776746,POR rs10954732,ABCB1 rs1045642,NR1I2 rs7643645突变等位基因均可导致VRZ血药浓度降低,ABCC2 rs717620突变等位基因…
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Background: Pharmacogenetic markers associated with the need to switch patients from methotrexate (MTX) to biologic agents in moderate-to-severe psoriasis remain insufficiently …
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… identified, where 4 focused on ABCC2 rs717620, 3 on rs2273697, and 3 on rs3740066, as shown in Table 2 . Based on the results, ABCC2 rs717620 showed that the presence of the …
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… Patients carrying the TT genotype of ABCC2 rs717620 had a 14-fold higher risk of developing hepatic ADR associated with elevated ALP levels. To the best of our knowledge, this is the …
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… and genotypes of ABCC2 rs717620 and ABCC4 rs2274407 were retained in the final model. CONCLUSION: Age, BSA, SCr and genotypes of ABCC2 rs717620 and ABCC4 rs2274407 …
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… The panels show: (A) rs717620 genotype and ABCC2 expression in the cerebellum; (B) rs717620 genotype and ABCC2 expression in the cerebellar hemisphere; (C) rs3740066 …
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… The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type… mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration. …
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… explored the impact of genetic variations affecting the gene coding for ABCC2 (rs717620, … vary significantly in association with SNPs rs717620, rs2273697 and rs3740066, respectively. …
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High-dose methotrexate (HDMTX) is the cornerstone of the treatment for primary central nervous system lymphoma (PCNSL). The prevention of drug-induced toxicities is critical. This study aims to identify key factors associated with HDMTX-induced toxicities (hematotoxicity, hepatotoxicity and nephrotoxicit) in 713 Chinese PCNSL patients undergoing 3021 HDMTX treatment courses. Demographic data, administration information, laboratory tests, area under the curve, co-medications, and 30 single nucleotide polymorphisms were collected to analyze the association of HDMTX-related toxicities using PLINK and SPSS. Higher ALB level, female, ABCB1 rs1045642, MTHFR rs1801131, and MTHFD1 rs2236225 were associated with lower risk of anemia, while the combination of furosemide, torasemide, bumetanide, and levetiracetam associating with higher risk. Co-use of torasemide had higher incidence of neutropenia. Higher level of ALB was correlated with less leukopenia; torasemide and rs2236225 were related to more leukopenia. Female, furosemide, rs1801133, ABCG2 rs2231142, ABCC2 rs717620 were related to more thrombocytopenia, while rs1045642 and high ALB were related to less. Rs1801131 and female were correlated with more hepatotoxicity, whereas furosemide was correlated with less. In nephrotoxicity, female and rs1801394 were correlated with less, MTHFR rs1801131 and rs1801133 were correlated with more. In conclusion, higher ALB levels had a lower risk of HDMTX toxicities; loop diuretics and levetiracetam generally accelerated the occurrence of toxicities. Rs1801133 GG, rs1128503 GG + AG, rs2231142 AA+ AC, rs717620 TT + GT were associated with increased risk of toxicity; rs1045642 TT and rs1801394 GG + AG were less likely to develop toxicity.
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To establish a population pharmacokinetic (PPK) model of high-dose methotrexate in pediatric patients with diverse malignancies.
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目的 探讨 X 射线修复交叉互补蛋白 1 (X-ray repair cross-complementing protein 1, XRCC1), 三磷酸腺苷结合转运蛋白 G 超家族成员 2 (ATP-binding cassette superfamily G member 2, ABCG2) 基因多态性与中晚期结直肠癌 (colorectalcancer, CRC) 患者铂类化疗敏感性的相关性. 方法 选择 2021 年 1 月至 2022 年 8 月温州医科大学附属平阳医院收治的 75 例中晚期 CRC 患者, 均采用铂类药物化疗方案治疗 24 周. 所有患者均于化疗前检测外周血 XRCC1-Rs25487 和 ABCG2-Rs717620 基因位点的多态性, 探究其与患者 2 年总生存率的关系, 采用比例风险 (Cox) 回归模型分析影响患者预后不良的因素. 结果 75 例中晚期 CRC 患者的化疗总有效率为 52.00%(39/75). XRCC1-Rs25487 基因型中, AA 基因型携带者对铂类药物的化疗敏感性较 GG+ GA 基因型携带者的化疗敏感性更低 (P< 0.05); ABCG2-Rs717620 基因型中, TT 基因型携带者对铂类药物的化疗敏感性较 CC+ CT 基因型携带者的化疗敏感性更低 (P< 0.05). Kaplan-Meier 分析显示, XRCC1-Rs25487 位点基因 GA/GG 型中位生存时间长于 AA 型; ABCG2-Rs717620 位点基因 CC/CT 型中位生存时间长于 TT 型 (P< 0.05). 多因素 Cox 分析显示, 铂类药物化疗效果和 XRCC1-Rs25487 位点基因 AA 型, ABCG2-Rs717620 位点基因 TT 型均为中晚期 CRC 患者铂类药物化疗后 2 年总生存率的独立影响因素 (P< 0.05). 结论 XRCC1, ABCG2 基因多态性与中晚期 CRC 患者铂类药物化疗敏感性有关, XRCC1-Rs25487GG/GA 基因型和 ABCG2-Rs717620 CC/CT 基因型可为中晚期 CRC 患者铂类化疗带来更好的药物敏感性和生存期. (To explore the correlation between polymorphisms in the X-ray repair cross-complementing protein 1 (XRCC1) and ATP-binding cassette superfamily G member 2 (ABCG2) genes and the sensitivity to platinum-based chemotherapy in patients with advanced colorectal cancer (CRC). Methods A total of 75 patients with advanced CRC admitted to Pingyang Hospital Affiliated to Wenzhou Medical University between January 2021 and August 2022 were enrolled, all of them received platinum-based chemotherapy for 24 weeks. Before chemotherapy, polymorphisms of peripheral blood XRCC1-Rs25487 and ABCG2-Rs717620 were detected, and their relationship with 2-year overall survival rate was explored. The influencing factors of poor prognosis were analyzed by proportional hazards (Cox) regression model. Results The overall response rate to chemotherapy was 52.00%(39/75) among the 75 patients. In XRCC1-Rs25487 genotypes, sensitivity to platinum-based chemotherapy in AA genotype was lower than that in GG+ GA genotype (P< 0.05). In ABCG2-Rs717620 genotypes, sensitivity to platinum-based chemotherapy in TT genotype was lower than that in CC+ CT genotype (P< 0.05). Kaplan-Meier analysis showed that in XRCC1-Rs25487, median survival time of GA/GG genotype was longer than that of AA genotype. In ABCG2-Rs717620, median survival time of CC/CT genotype was longer than that of TT genotype (P< 0.05). Multivariate Cox analysis showed that platinum-based chemotherapy response, AA genotype of XRCC1-Rs25487 and TT genotype of ABCG2-Rs717620 were independent influencing factors of 2-year overall survival rate in patients with advanced CRC after platinum-based chemotherapy (P< 0.05). Conclusion Polymorphisms in the XRCC1 and ABCG2 genes are associated with sensitivity to platinum-based chemotherapy in patients with advanced CRC. XRCC1-Rs25487 GG/GA genotypes and ABCG2-Rs717620 CC/CT genotypes can provide better sensitivity to platinum-based chemotherapy and survival for patients with advanced CRC.)
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24 25 Supplementary Figure 1. Functional annotation (in terms of biological processes) of the 26 genes putatively associated with (poly) phenol metabolism investigated in the studies included 27 in the present systematic review. Nodes in the diagram are color-coded according to their p-28 value (yellow-to-red according to increasing statistical significance). Genes in the GO tree 29 are associated with the GO term (s) to which they are directly annotated (biological 30 processes). Only significant hits with a p-value≤ 0.01 and terms descended from them are 31 included.
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Response to (poly)phenol intake is highly variable among subjects, and genetic variants may contribute to such variability. However, evidence addressing this assumption is currently lacking. To address such shortcomings, we systematically reviewed the current literature and selected twelve studies looking at associations between the inter-individual variability in (poly)phenol bioavailability and metabolism and single nucleotide polymorphisms (SNPs) in candidate genes involved in (poly)phenol ADME (absorption, distribution, metabolism, and excretion). In total, 88 SNPs in 33 genes were studied, of which slightly more than half (n = 17) were related to drug/xenobiotic metabolism. More specifically, two were involved in absorption, seven in phase I metabolism, four in phase II metabolism, and four in excretion. The remaining 16 genes were related to steroid hormone metabolism and activity. Considering genes specifically related to (poly)phenol ADME, 16 SNPs showed significant modifying effects on urinary and/or plasma levels of phenolic metabolites and/or on their kinetic parameters. However, it was not possible to associate a particular genetic variant with a change in (poly)phenol-related ADME. Only a few studies applied stringent statistical criteria and recruited sufficiently large and diverse samples to reach solid and reliable conclusions. As such, studies employing larger samples, leveraging integrative bioinformatics approaches and genome-wide linkage, are warranted.
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High‐dose methotrexate (HD‐MTX) infusions are commonly used to consolidate remission in children with acute lymphoblastic leukemia (ALL). We investigate the potential role of candidate polymorphisms in SLCO1B1 (rs4149056 and rs2306283), ABCB1 (rs1045642), ABCC2 (rs717620), ABCC3 (rs9895420), and ABCC4 (rs7317112) drug transporters genes on HD‐MTX pharmacokinetics and patients' outcome (meant both as relapse and drug‐related toxicities) in an Italian cohort of 204 ALL pediatric patients treated according to the AIEOP‐BFM ALL 2009 protocol. TaqMan SNP genotyping assays determined patient's genotypes. Measurements of HD‐MTX plasma concentration were available for 814 HD‐MTX courses in 204 patients; MTX clearance was estimated by a two‐compartmental linear pharmacokinetic model with first‐order elimination and a Bayesian approach, via ADAPT. Independent contributions of age and ABCC4 SNP rs7317112 (A>G, intronic) on MTX clearance were detected in a multivariate analysis (p = 1.57 × 10−8 and p = 2.06 × 10−5, respectively), suggesting a delayed elimination of the drug in older patients and an accelerated one in carriers of the variant GG genotype. After multiple corrections, the association between ABCC2 SNP rs717620 (−24 C>T) and severe hematological toxicity was found (p < 0.005). Moreover, SLCO1B1 SNP rs4149056 (c.521T>C, p.V174A) affected patients' outcomes: carriers of the variant C allele presented a reduced risk of relapse compared to wild‐type TT (hazard risk: 0.27, 95% confidence interval [CI]: 0.08–0.90, p = 0.037). Taken together, these data highlighted the importance of variants in drug transporters genes on HD‐MTX disposition in the AIEOP‐BFM ALL 2009 protocol consolidation phase, and their putative role as predictive markers of outcome.
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Irinotecan treatment is often complicated by gastrointestinal, hematological, and infusion-related toxicities, the latter of which typically presents as acute cholinergic syndrome (ACS). While genetic variation in UGT1A1 increases toxicity risk, fewer studies have investigated variation in other genes. This study aimed to assess the impact of variation in other genes involved in irinotecan pharmacokinetics with irinotecan-related toxicity. This was a retrospective study of patients receiving standard irinotecan doses (180 mg/m 2 ) with available genetic and clinical data. The primary analysis was to investigate the impact of carboxylesterase (CES) genetic variation on irinotecan infusion-related ACS. Exploratory secondary analyses evaluated variation in CES1 , CES2 , UGT1A7 , UGT1A9 , ABCB1 , ABCG2 , ABCC2 , and SLCO1B1 with severe toxicity, treatment modification, diarrhea, and neutropenia. Univariate associations with P less than 0.05 were adjusted for UGT1A1 *28 and UGT1A1 *6 genotype. A total of 93 patients were included in this analysis. CES1 variants were not associated with infusion-related ACS. In the exploratory analysis, CES1 rs3785161 AA was associated with an increased likelihood of severe irinotecan toxicity (37 vs. 16%; P = 0.034), and ABCG2 rs2231142 AA/AC was associated with an increased likelihood of severe neutropenia (33 vs. 8%; P = 0.017). CES1 and ABCG2 variants may increase the risk of irinotecan toxicity. Further studies are needed to validate these associations to justify prospective studies investigating the clinical benefits of genetics-guided irinotecan dosing.
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To develop a population pharmacokinetic (PPK) model for methotrexate (MTX) dosage for all ages, assess the association between concentration and clearance, and …
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… ABCC2 −24C>T (rs717620) is associated with reduced expression of this transporter protein (20). ABCG2 421C>A (Gln141Lys, rs2231142) is related to the reduced expression of the …
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Вступ. Наразі інгібітори гідроксиметилглутарил-коензим А-редуктази (статини) є одними з найбільш поширених гіполіпідемічних лікарських засобів в усьому світі. Однак, на …
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… Only rs717620 in ABCC2 was marginally associated with the NSAID risk. iSAEC NSAID-DILI patients did show a significantly increased frequency of carrying the PTPN22 missense …
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Lung cancer has the highest mortality rate among all the highly prevalent neoplasia globally. The major concern with its frontline treatment-cisplatin, is the rapid progression of …
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Concomitant high‐dose cisplatin with radiotherapy is commonly used for treating head and neck squamous cell carcinoma (HNSCC). Cisplatin, often used with radiotherapy…
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Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (…
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Human immunodeficiency virus (HIV) and tuberculosis (TB) are major contributors to morbidity and mortality in sub-Saharan Africa including Cameroon. Pharmacogenetic …
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… The frequently investigated genetic polymorphisms in ABCC2 were rs717620 (C-24T) (n = 6), rs3740066 (C3972T, Ile1324Ile) (n = 5), rs2273697 (G1249A) (n = 4), rs12762549(*+…
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Investigate the role of host genetic variations in high-risk human papillomaviruses (HR-HPVs). Methods: This cross-sectional study recruited 238 cervical cancer patients. Variants …
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… Differences in MAF frequencies of rs3740066 and rs717620 between Roma and 1000 Genomes populations of European-origin suggest that adverse drug effects should be considered …
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… 24C >T polymorphism (rs717620), which causes reduced protein expression, has been the most studied, especially concerning cytostatics efficacy and safety [17]. As indicated by …
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… rs717620, rs3740065 and rs3740066 is a research hotspot. The study reported that the wild type of ABCC2 rs717620 … CT/TT genotype of ABCC2 rs717620 was significantly higher than …
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It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c. 521T> C differ from …
75
Platinum-based chemotherapy (PBC) is a widely used treatment for various solid tumors, including non-small cell lung cancer (NSCLC). However, its efficacy is often compromised by …
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The widespread clinical use of lacosamide (LCM) has revealed significant individual differences in clinical response, with various reported influencing factors. However, it …
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Influência das variantes genéticas nos transportadores de efluxo em genes da familia ABC nas reações adversas e sobrevida em pacientes com câncer de pulmão …
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… The rs717620 T allele in ABCC2 significantly increased the MTX concentration by affecting its ability to transport MTX out of cells [54]. This could be because this polymorphism …
79
Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of …
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… The drug transporters ABCC2 rs717620 variant allele and ABCG2 rs2231142 variant allele were both found to be significantly associated with protective effects against PBC …
81
… -1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and …
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Wuzhi capsule (WZC), a commonly used Chinese patent medicine to treat various types of liver dysfunction in China, increases the exposure of tacrolimus (TAC) in liver transplant …
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The ABCC2 gene encodes the multidrug resistance-associated protein 2, MRP2, an ATP-binding cassette transporter that plays an important role in detoxification and chemoprotection, …
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… rs717620, a multiple linear regression model was used in which rs8187710 and rs717620 … P value is 0.015 significant while Pearson correlation rs717620 is –0.045 weak correlation. …
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… Based on the existing literature and the genotype of our patient, heterozygous for both ABCC2 rs717620 (c.-24C>T) and ABCC2 rs2273697 (c.1249G>A), it seems plausible to suggest …
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… Here we present evidence that rs717620 regulates ABCC2 expression in multiple brain regions, suggesting that rs717620 may influence the efficacy of ASM therapy by regulating …
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Pediatric epilepsy is a complicated neuropsychiatric disorder that is characterized by recurrent seizures and unusual synchronized electrical activities within brain tissues. It has a substantial effect on the quality of life of children, thus understanding of the hereditary considerations influencing epilepsy susceptibility and the response to antiepileptic medications is crucial. This study focuses on assessing the correlation of the ABCB1, ABCC2, CYP1A2, and CYP2B6 genetic polymorphisms with the susceptibility to epileptic seizures and their contributions to antiepileptic medication throughout the course of the disease.
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Microbiota-derived toxins indoxyl sulfate and hippuric acid were previously reported to be associated with altered pharmacokinetics of the immunosuppressant tacrolimus in liver transplant recipients, and ABC transporter proteins are likely to be involved in the transport of such substances, but the in vivo role has not been elucidated. The aim of this study was to assess the retention of indoxyl sulfate and hippuric acid in the plasma of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 (changes in transporter activity due to genetic variation), and to explore whether genetic variation is involved in altering the relationship between microbe-derived toxins and tacrolimus pharmacokinetics. Methods Liver transplantation subjects treated with the immunosuppressive regimen tacrolimus, corticosteroids, and mycophyolate mofetil were included and divided into normal renal function group and chronic kidney disease group. The plasma concentrations of indoxyl sulfate and hippuric acid in two groups of liver transplantation subjects carrying different genotypes of ABCB1 and ABCC2 were compared. For genotype carriers with significant differences, the Pearson Correlation Coefficient method was further used to investigate the correlation between plasma indoxyl sulfate level and tacrolimus dose-corrected trough concentration in patients with different renal function status. Results Carriers of the rs717620-24T variant exhibited high plasma indoxyl sulfate retention in patients with normal renal function, and furthermore, chronic kidney disease patients and patients with normal renal function exhibited indoxyl sulfate and tacrolimus in the ABCC2 normal function (β = −0.740, p = 0.020) and reduced function groups (β = −0.526, p = 0.005), respectively, showing a strong correlation with tacrolimus. Conclusion ABCC2 may be one of the pathways by which tacrolimus pharmacokinetics is altered by indoxyl sulfate.
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Although it is traditionally believed that ATP binding cassette subfamily C member 2 (ABCC2) is a multidrug resistance‐associated protein correlated with a worse prognosis, our previous and several other studies demonstrated the contrary to be true in gastric cancer (GC). We aim to explore the underlying mechanism of this discovery. Methods Our study utilized whole‐exome sequencing (WES), RNA sequencing, and droplet digital PCR (ddPCR) analysis of 80 gastric cancer samples, along with comprehensive immunohistochemical (IHC) analysis of 1044 human GC tissue samples.By utilizing CRISPRCas9 to genetically modify cell lines with the ABCC2‐24C > T (rs717620) point mutation and conducting dual‐luciferase reporter assays, we identified that transcription factors SOX9 and ETS1 serve as negative regulators of ABCC2 expression. Seahorse assay and mass spectrometry were used to discover altered metabolic patterns. Gain and loss‐of‐function experiments in GC cell lines and preclinical models were carried out to validate ABCC2 biological function. Results ABCC2 high expression correlated with better prognosis, and rs717620 can influence ABCC2 expression by disrupting the binding of ETS1 and SOX9. Gain and loss‐of‐function experiments in GC cell lines demonstrated amino acid deprivation reduces proliferation, migration, and drug resistance in ABCC2‐high GC cells. ABCC2 leads to reduced intracellular amino acid pools and disruption of cellular energy metabolism. This phenomenon depended on ABCC2‐mediated GSH extrusion, resulting in alterations in redox status, thereby increasing the cell's susceptibility to ferroptosis. Furthermore, patient‐derived organoids and patient‐derived tumor‐like cell clusters were used to observe impact of ABCC2 on therapeutic effect. In the xenograft model with high ABCC2 expression, we observed that constricting amino acid intake in conjunction with GPX4 inactivation resulted in notable tumor regression. Conclusions Our findings demonstrate a significant role of ABCC2 in amino acid metabolism and ferroptosis by mediating GSH efflux in GC. This discovery underlines the potential of combining multiple ferroptosis targets as a promising therapeutic strategy for GC with high ABCC2 expression. Highlights ABCC2 plays a crucial role in inducing metabolic vulnerability and ferroptosis in gastric cancer through enhanced glutathione efflux. The ABCC2 24C > T polymorphism is a key factor influencing its expression. These results highlight the potential of ABCC2 as a predictive biomarker and therapeutic target in gastric cancer.
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Statins are well known for their efficacy to improve lipid profiles. Their efficacy varies between individuals and can be modified by patient factors such as genetic polymorphisms. This study used a cross-sectional retrospective design to assess the effect of selected single nucleotide polymorphisms (SNPs) and other patient-specific clinical variables on statin-related lipid profile changes in a subgroup of Malaysians. The impact of low and moderate intensity of statin doses (10–40 mg/day for at least six weeks), regardless of statin types, was assessed between SNPs of previously identified genes with clinical relation to statin efficacy and lipid profile changes before (baseline) and after statin treatment; two ranges of treatment durations, i.e. ≤ 6 months and 7–12 months. DNA was extracted from patient's venous blood (3 mL), and SNP genotyping was performed using PCR–RFLP method. Using a dominant genetic model, the association between selected SNPs from six genes of interest ( ABCG2 , ABCC2 , APOE , APOA5 , GATM and COQ2 ) and the patients' lipid profiles was investigated. Results A total of 229 statin-treated patients were included. The mean age of the patients was 53 ± 7.16 years, and they were mostly females (53.3%), Malay (96.1%), and were taking atorvastatin and simvastatin (90.4%). Seven SNPs genotyped from six genes investigated were related to different lipid profile before and after statin treatment. At baseline, ABCG2 rs2231142 ( P = 0.035) and APOA5 rs662799 ( P = 0.007) variants had higher HDL-c levels, while ABCC2 rs717620 variants had higher TC ( P = 0.040) and LDL-c levels ( P = 0.022). Following statin treatment, ABCC2 rs717620 (lower TG, P = 0.009) and APOA5 rs662799 (higher HDL, P = 0.031; lower TG, P = 0.037) were associated with improved lipid profiles, with the association being substantially related to males carrying minor alleles of the SNPs. None of the investigated SNPs were related to significant statin-related LDL-c lowering effects during statin therapy. Conclusion To better understand inter-individual heterogeneity in lipid profiles during statin therapy, it would be helpful to take patient genetics and gender into consideration before and after administering statins.
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… One cohort study from Slovenia demonstrated that polymorphism of ABCC2 (rs717620) presented an insufficient response to MTX treatment (75% reduction from baseline PASI score (…
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Methotrexate (MTX) is subject to therapeutic drug monitoring because of its high pharmacokinetic variability and safety risk outside the therapeutic window. This study aimed …
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The use of pharmacogenetic guidelines in personalizing treatments has shown the potential to reduce interindividual variability in drug response by enabling genotype-matched dosing …
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Urinary bladder cancer (UBC) holds a potentially profound social burden and affects over 573,278 new cases annually. The disease’s primary risk factors include occupational tobacco …
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Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how …
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… (p<0.05) overrepresentation of CYP2C19 intermediate metabolisers (IM) and CYP2C19*2 allele, and under-representation of CYP2C19 rapid metabolisers (RM) and ABCC2 rs717620. …
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… The ABCC2 gene encodes a transporter protein that has a tremendous impact on the transport and clearance of VRZ, and the rs717620 polymorphic locus CT + TT allele carrying the …
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… At the same time, a few abnormalities also emerged in terms of disease and syndrome (eg, Dubin-Johnson syndrome caused by the presence of rs717620). Though these SNPs belong …
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Heart transplantation (HT) remains the optimal therapy for patients living with end-stage heart disease. Despite recent improvements in peri-transplant management, …
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This chapter is devoted to drug-resistant epilepsy and its genetic mechanisms. There are currently six hypotheses proposed for pharmacoresistant epilepsy. The genetic aspects of five …
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… 解析対象の遺伝子多型は SLC31A1 rs10981694A>C,rs12686377G>T,ATP7B rs9535828A>G,GSTP1 rs1695A>G および ABCC2 rs717620 (−24C>T)とした.白金製剤+5-FU 併用療法施行後…
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The potential implication of MDR1 and NAC1 genetic polymorphisms on resistance to antiepileptic drugs among a Jordanian epileptic population: a cross-sectional study …
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We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African …
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Adenosine triphosphate (ATP)-binding cassette (ABC) transporters play an important role in the response to methotrexate (MTX). In this study, we investigated the frequency …
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Human intoxication to mercury is a worldwide health problem. In addition to the type and length of exposure, the genetic background plays an important role in mercury poisoning. …
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… the CC genotype for the ABCC2 (encoding MRP-2) 224C>T rs717620 SNP was associated with higher tenofovir …
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… [50] found that combined UGT1A9-440T>C, UGT2B7 rs7438135, and ABCC2 rs717620 polymorphisms might be important predictors of inter-individual variability in MPA exposure in …
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To evaluate the association between CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic …
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Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide …
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Context Statins are the lipid-lowering therapy of choice for the prevention of atherosclerotic cardiovascular disease (ASCVD) but their effectiveness in lowering low-density lipoprotein …
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… [28], the ABCC2 (MRP2) rs717620 T variant was associated with an increased risk of hyperbilirubinemia and mortality in patients with iDILI, confirming that ABC transporter genetic …
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Deferasirox is an iron-chelating agent prescribed to patients with iron overload. Due to the interindividual variability of deferasirox responses reported in various populations, …
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This study aimed to establish a population pharmacokinetic (PPK) model of mycophenolic acid (MPA), quantify the effect of clinical factors and pharmacogenomics of MPA, and optimise …
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… On the other hand, in another study, the change in LDL-C was more pronounced among patients who carried both the variant allele for rs717620 in ABCC2 gene and wild-type allele for …
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This study was designed to analyze the correlation between single nucleotide polymorphisms (SNP) related to drug metabolism and pharmacokinetics of mycophenolic acid (…
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… ABCC2 rs717620 correlated with MTX plasma concentration at 48 h after the start of infusion [Citation22]. Thus far, few studies have focused on the relationship between genetic …
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… However, the genetic polymorphism ABCC2 (rs717620) has a functional effect associated with a decrease in tenofovir-induced kidney tubular dysfunction (12). Moss et al. attribute this …
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… carcinoma were identified in the ABBC2 gene group (rs717620) and 1 case (4.16%) in the … due to various causes, in the ABCC2 gene (rs717620), and a higher prevalence of the A/A …
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… The MAF value for ABCC2 rs717620 T was also very low in this study (2.8%), … These results for both SLCOB1 rs4149056 and ABCC2 rs717620 suggest that there will be no …
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… rs717620, have been confirmed as contributing to the variability of MTX kinetics.23 However, the influence of ABCC2 rs717620 … ,27 The effects of ABCC2 rs717620 on MTX metabolism …
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Purpose: We aimed to evaluate the effect of the ABCC2 1249G> A (rs2273697) and− 24C> T (rs717620) polymorphisms on lacosamide (LCM) plasma concentrations and the efficacy of …
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Akutna limfoblastna levkemija predstavlja 80% vseh primerov levkemij otroške populacije. Bolniki med najdaljšo, vzdrževalno fazo zdravljenja prejemajo dnevne odmerke 6-merkaptopurina in tedenske odmerke metotreksata, ki so izračunani glede na telesno površino pacientov in se prilagajajo glede na koncentracije levkocitov ter pojavljanje hudih neželenih učinkov. Posamezniki se na tako predpisano terapijo odzivajo precej raznoliko. Za pojasnitev tovrstne interindividualne variabilnosti v odzivu na tiopurinsko terapijo smo v študiji na slovenski pediatrični populaciji preučevali vpliv potencialnih genetskih in drugih dejavnikov na varnost in učinkovitost vzdrževalne terapije akutne limfoblastne levkemije. Kandidatni geni so bili nosilci zapisa za encime v metabolizmu 6-merkaptopurina, čezmembranskem transportu metotreksata, v folatnem in metioninskem ciklu. Potek vzdrževalne terapije smo ovrednotili z izračunom razmerja med prejetim in izračunanim odmerkom 6-merkaptopurina, tako na dnevni ravni kot na ravni kumulativnih odmerkov med vzdrževalno terapijo. Pred uvedbo Bonferroni korekcije za multiplo testiranje sta bila variantna alela v ABCC2 (rs717620) in MTHFD1 (rs2236225) po dominantnem modelu povezana s prejemanjem višjih odmerkov od izračunanih. ABCC2 (rs717620) je ostal značilen dejavnik poteka tiopurinske terapije tudi po pretvorbi razmerja na ravni kumulativnih odmerkov v kategorično spremenljivko (fenotipsko slabi presnavljalci pod 0, 9; med 0, 9 in 1, 1 fenotipsko normalni presnavljalci ter nad 1, 1 fenotipsko hitri presnavljalci). V genu TPMT, ki je glavni farmakogenetski dejavnik tiopurinske terapije, najpogostejših klinično pomembnih alelov TPMT* 3C, TPMT* 3A in TPMT* 2 nismo našli. S sekvenciranjem naslednje generacije smo med 6 različicami, ki so že poročane v farmakogenetski bazi PharmGKB, našli eno sinonimno različico (rs17839843), ki bi lahko bila povezana s povečano encimsko aktivnostjo. Dodatno smo identificirali še 4 intronske različice, ki še niso bile poročane v bazi PharmGKB, in sta jih vsaj 2 napovedna modela v bioinformacijskem orodju PredictSNP označila kot škodljive (rs114611199, rs146407521, rs2518469 in rs1024721139). Nadalje smo prvič v slovenski populaciji bolnikov z akutno limfoblastno levkemijo določali prisotnost različic v genu NUDT15 in določili 4 polimorfizme v odsekih, ki vključujejo ekson 1 in 3 (rs45465203, rs116855232, rs61746486, rs116855232). Po analizi z napovednimi modeli in spletnimi bazami podatkov sta se kot najpomembnejši izkazali intronski različici rs45465203 in drugačnosmiselna različica rs116855232. Frekvenci variantnih alelov rs61746486 in rs116855232 sta za faktor 10 višji od tistih, poročanih v literaturi za splošno evropsko populacijo. Med negenetskimi dejavniki je s potekom vzdrževalne tiopurinske terapije povezana razvrstitev v skupino tveganja, kjer skupini s standardnim in srednjim tveganjem prejmeta odmerke značilno bližje predvidenim kot v skupini z visokim tveganjem. Na 15 preiskovancih smo razvili preliminarni napovedni model za vrednost razmerja med prejetimi in izračunanimi kumulativnimi odmerki 6-merkaptopurina, ki po metodi izbora najprimernejšega modela AIC vsebuje spremenljivke skupina tveganja IR in HR, genotip MTHFD1 (rs2236225) po dominantnem modelu in prilagojeno vsoto variantnih alelov TPMT. Ugotovitve in opažanja v magistrski nalogi so lahko smernice za nadaljnje raziskave na večjem vzorcu bolnikov.
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Akutna limfoblastna levkemija predstavlja 80% vseh primerov levkemij otroške populacije. Bolniki med najdaljšo, vzdrževalno fazo zdravljenja prejemajo dnevne odmerke 6-merkaptopurina in tedenske odmerke metotreksata, ki so izračunani glede na telesno površino pacientov in se prilagajajo glede na koncentracije levkocitov ter pojavljanje hudih neželenih učinkov. Posamezniki se na tako predpisano terapijo odzivajo precej raznoliko. Za pojasnitev tovrstne interindividualne variabilnosti v odzivu na tiopurinsko terapijo smo v študiji na slovenski pediatrični populaciji preučevali vpliv potencialnih genetskih in drugih dejavnikov na varnost in učinkovitost vzdrževalne terapije akutne limfoblastne levkemije. Kandidatni geni so bili nosilci zapisa za encime v metabolizmu 6-merkaptopurina, čezmembranskem transportu metotreksata, v folatnem in metioninskem ciklu. Potek vzdrževalne terapije smo ovrednotili z izračunom razmerja med prejetim in izračunanim odmerkom 6-merkaptopurina, tako na dnevni ravni kot na ravni kumulativnih odmerkov med vzdrževalno terapijo. Pred uvedbo Bonferroni korekcije za multiplo testiranje sta bila variantna alela v ABCC2 (rs717620) in MTHFD1 (rs2236225) po dominantnem modelu povezana s prejemanjem višjih odmerkov od izračunanih. ABCC2 (rs717620) je ostal značilen dejavnik poteka tiopurinske terapije tudi po pretvorbi razmerja na ravni kumulativnih odmerkov v kategorično spremenljivko (fenotipsko slabi presnavljalci pod 0, 9; med 0, 9 in 1, 1 fenotipsko normalni presnavljalci ter nad 1, 1 fenotipsko hitri presnavljalci). V genu TPMT, ki je glavni farmakogenetski dejavnik tiopurinske terapije, najpogostejših klinično pomembnih alelov TPMT* 3C, TPMT* 3A in TPMT* 2 nismo našli. S sekvenciranjem naslednje generacije smo med 6 različicami, ki so že poročane v farmakogenetski bazi PharmGKB, našli eno sinonimno različico (rs17839843), ki bi lahko bila povezana s povečano encimsko aktivnostjo. Dodatno smo identificirali še 4 intronske različice, ki še niso bile poročane v bazi PharmGKB, in sta jih vsaj 2 napovedna modela v bioinformacijskem orodju PredictSNP označila kot škodljive (rs114611199, rs146407521, rs2518469 in rs1024721139). Nadalje smo prvič v slovenski populaciji bolnikov z akutno limfoblastno levkemijo določali prisotnost različic v genu NUDT15 in določili 4 polimorfizme v odsekih, ki vključujejo ekson 1 in 3 (rs45465203, rs116855232, rs61746486, rs116855232). Po analizi z napovednimi modeli in spletnimi bazami podatkov sta se kot najpomembnejši izkazali intronski različici rs45465203 in drugačnosmiselna različica rs116855232. Frekvenci variantnih alelov rs61746486 in rs116855232 sta za faktor 10 višji od tistih, poročanih v literaturi za splošno evropsko populacijo. Med negenetskimi dejavniki je s potekom vzdrževalne tiopurinske terapije povezana razvrstitev v skupino tveganja, kjer skupini s standardnim in srednjim tveganjem prejmeta odmerke značilno bližje predvidenim kot v skupini z visokim tveganjem. Na 15 preiskovancih smo razvili preliminarni napovedni model za vrednost razmerja med prejetimi in izračunanimi kumulativnimi odmerki 6-merkaptopurina, ki po metodi izbora najprimernejšega modela AIC vsebuje spremenljivke skupina tveganja IR in HR, genotip MTHFD1 (rs2236225) po dominantnem modelu in prilagojeno vsoto variantnih alelov TPMT. Ugotovitve in opažanja v magistrski nalogi so lahko smernice za nadaljnje raziskave na večjem vzorcu bolnikov.
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This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer.
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Renal toxicity is more common with tenofovir disoproxil fumarate (TDF) than with tenofovir alafenamide fumarate (TAF). We investigated whether polymorphisms in genes relevant to tenofovir disposition affect renal toxicity among HIV-positive Southern Africans. Methods Genetic sub-study of adults randomized to initiate TAF or TDF together with dolutegravir and emtricitabine was conducted. Outcomes were changes from week 4 to 48 in the estimated glomerular filtration rate (eGFR) and from baseline to week 48 in urine retinol-binding protein and urine β2-microglobulin adjusted for urinary creatinine (uRBP/Cr and uB2M/Cr). Primary analyses prioritized 14 polymorphisms previously reported to be associated with tenofovir disposition or renal outcomes, and all polymorphisms in 14 selected genes. We also explored genome-wide associations. Results 336 participants were enrolled. Among 14 polymorphisms of primary interest, the lowest P values for change in eGFR, uRBP/Cr, and uB2M/Cr were ABCC4 rs899494 (P = 0.022), ABCC10 rs2125739 (P = 0.07), and ABCC4 rs1059751 (P = 0.0088); and in genes of interest, the lowest P values were ABCC4 rs4148481 (P = 0.0013), rs691857 (P = 0.00039), and PKD2 rs72659631 (P = 0.0011). However, none of these polymorphisms withstood correction for multiple testing. Genome-wide, the lowest P values were COL27A1 rs1687402 (P = 3.4 × 10−9), CDH4 rs66494466 (P = 5.6 × 10−8), and ITGA4 rs3770126 (P = 6.1 × 10−7). Conclusion Two ABCC4 polymorphisms, rs899494 and rs1059751, were nominally associated with change in eGFR and uB2M/Cr, respectively, albeit in the opposite direction of previous reports. COL27A1 polymorphism was genome-wide significantly associated with change in eGFR.
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Simple Summary Vincristine is a drug that is part of the treatment for many children with cancer. Its main side-effect is vincristine-induced peripheral neuropathy (VIPN), which often …
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Antioxidants are molecules characterized by function rather than common structural motifs. Their common feature is the capability of acting “anti”-oxidants in biological systems. Owing …
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… A significant association was found between response to Dox therapy and the rs717620 polymorphism of the ABCC2 gene. The presence of this gene variant resulted in the reduced …
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Antioxidants are molecules characterized by function rather than common structural motifs. Their common feature is the capability of acting “anti”-oxidants in biological systems. Owing …
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Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children between the ages of 2 and 6. It is more frequent in boys than in girls. Currently, the overall cure rate …
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Antioxidants are molecules characterized by function rather than common structural motifs. Their common feature is the capability of acting “anti”-oxidants in biological systems. Owing …
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Cinitapride is a gastrointestinal prokinetic drug, prescribed for the treatment of functional dyspepsia, and as an adjuvant therapy for gastroesophageal reflux disease. In this study, we …
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As a chronic brain disease, epilepsy affects ~50 million people worldwide. The traditional antiepileptic drugs (AEDs) are widely applied but showing various problems. Although the new …
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Cisplatin (CDDP) is a drug for high-grade osteosarcoma (HGOS) treatment. Several germline pharmacogenetic studies have revealed associations between single nucleotide …
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Platinum-induced nephrotoxicity is a severe and unexpected adverse drug reaction that could lead to treatment failure in non-small cell lung cancer patients. …
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… well as rs717620 had no influence on PK and PD. Another study in 107 Spanish healthy participants found there was no association between ABCC2 rs2273697 and rs717620 and PK. …
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… (rs717620 and rs2273697) are conflicting, which complicates their evaluation. A study from Madrid (n=115) suggested a strong link between rs717620 … a possession of rs717620 and …
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The purpose of this study was to identify genetic variations associated with the metabolism of dabigatran in healthy Chinese subjects, with particular focus given to …
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… rs717620 可致外排蛋白表达增加,引起他莫昔芬活 性代谢物在胞内和血浆水平的有效浓度降低 ,导致 治疗失败和患者术后复发[15].肺癌中,ABCC2等位 基因变异与化疗药物诱导的毒性和生存…
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… In contrast, patients carrying the T allele of ABCC2 rs717620, when compared to CC homozygotes, showed decreased estimated glomerular filtration rate [50]. In turn, the analysis of the …
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… Citation40 It has been reported that ABCC2 rs717620 was associated with response to platinum-based chemotherapy and pediatric heart transplant (PHTx). Citation30,Citation41,…
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Methotrexate (MTX) is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, its toxicity and efficacy varied greatly …
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Use of pharmacogenetics (PGx) tests to guide clinical decisions and care is appealing. From a broad perspective, this approach is intended to predict drug efficacy and adverse effects …
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… ABCC2 rs3740066 is in linkage disequilibrium with the rs717620 promoter variant that has been associated with reduced promoter activity and with lower ABCC2 mRNA levels [31,40], …
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This is a prospective cohort study with consecutive sam- pling. Blood samples were collected from patients with HNC tre Page 1 Methods: This is a prospective cohort study …
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Antioxidants are molecules characterized by function rather than common structural motifs. Their common feature is the capability of acting “anti”-oxidants in biological systems. Owing …
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… The ABCC2 rs717620 polymorphism was significantly associated with OS and DFS so that the GA+AA variant was associated with poor OS and DFS compared to the GG genotype [68]. …
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Rocuronium is widely utilized in clinical general anaesthesia, and individual differences in pharmacology and clearance have been observed. Two hundred thirty‐six Chinese patients …
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… A study of 190 Japanese patients found an association between TDF-induced renal tubular dysfunction and 2 ABCC2 polymorphisms (rs717620 and rs2273697).Disease was defined …
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This study aimed to identify physiological and pharmacogenomic covariates and develop a population pharmacokinetic model of high-dose methotrexate (HD-MTX) in Chinese …
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… we also confirmed that the variant ABCC2 rs717620 (c.-24C > … The rs717620 polymorphism is also known for its association … Our results for the two SNPs rs2273697 and rs717620 in the …
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High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-…
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Despite a dramatic increase in treatment options over the past 30 years, Carbamazepine (CBZ) is still considered the standard of care and the most prescribed initial treatment for focal …
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… results are presented in Table 1; briefly: whereas no statistically significant associations in patients with more advanced PDAC were observed, rs3740067, rs3740073 and rs717620 …
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… rs717620 可致外排蛋白表达增加,引起他莫昔芬活 性代谢物在胞内和血浆水平的有效浓度降低 ,导致 治疗失败和患者术后复发[15].肺癌中,ABCC2等位 基因变异与化疗药物诱导的毒性和生存…
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What is known and objective: Tacrolimus (TAC) is an immunosuppressant with large interpatient pharmacokinetic variability and a narrow therapeutic index. We report a case of acute …
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… El SNP rs1045642 del gen ABCB1 se ha asociado a una sobreexpresión de la glucoproteína P en la barrera hematoencefálica, de manera similar que el SNP rs717620 del gen …
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… Another candidate marker is rs717620 in ABCC2 5’UTR; rs717620-CT genotype showed a … and rs717620 variants in combination with others in haplotype arrangement (ie rs717620-T, …
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Oral mucositis (OM) is a painful inflammatory oral condition that affects children who undergo chemotherapy. Oxidative stress is a known OM mediator and pro-inflammatory cytokines …
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The aim of this study was to investigate the factors affecting the plasma concentration of oxcarbazepine (OXC) monotherapy in children with epilepsy. Methods: We recruited …
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… El SNP rs1045642 del gen ABCB1 se ha asociado a una sobreexpresión de la glucoproteína P en la barrera hematoencefálica, de manera similar que el SNP rs717620 del gen …
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Background. Tacrolimus has unpredictable pharmacokinetic (PK) characteristics, which are partially attributed to CYP3A5 polymorphism. The potential effects of clinical factors in the …
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… ABCC2 (rs717620) were associated with increased risk of treatment failure. Citation26 A study analyzing the drug survival of MTX in 117 patients showed ABCC2 rs717620 genotype …
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… than non-carriers, while the ABCC2 rs717620 and ABCC2 rs3740066 variants were not … treatment response was associated with ABCC2 rs717620 and ABCC2 rs3740066 variants. …
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Background There is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to …
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Head and neck cancer (HNC) is the set of malignant tumors located in the upper aerodigestive tract [1]. Treatment of locally advanced HNC is based on radiotherapy …
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… [ 10 ] showed an association of polymorphism (SNP) related to the ABCC2 gene, allele – 24C> T (rs717620) with PRTD related to the use of tenofovir. However, in a Japanese …
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… Analyze the frequency of polymorphism in the gene ABCC2 (rs717620) in those who had hematological and renal ADRs. Methods: Hematological and biochemical tests were …
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Clinical and genetic influencing factors on free fraction of mycophenolic acid (MPA) have rarely been discussed. The present study investigated whether the clinical and genetic factors …
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… O alelo variante de rs717620 foi associado neutropenia em graus acima de 1 (p= 0,040, OR= 0,261). O alelo ancestral de rs3740066 foi associado ao aumento da creatinina sérica em …
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… (rs717620 and rs2273697) are conflicting, which complicates their evaluation. A study from Madrid (n=115) suggested a strong link between rs717620 … a possession of rs717620 and …
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… These variants were CT in rs374066 and TC in rs717620, both in the recipient, which presented ORs of 0.920 (p-value = 0.017) and 0.878 (p-value = 0.012), respectively. On the other …
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… Selepas pesakit mengambil rawatan statin, dua SNPs (ABCC2 rs717620 and APOA5 rs662799) telah dikaitkan dengan kesan anti-aterogenik. ABCC2 rs717620 telah dikaitkan dengan …
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… ABCC2 (rs3740066, rs4148396 and rs717620) were significantly associated with clinical … composed of rs3740066, rs4148396 and rs717620 was found to be significantly associated …
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Now more than ever the pharmacovigilance has demonstrated great relevance in making medication safer by evaluating the benefit-risk ratio in the treatment used in COVID-19 patients [1]; nevertheless, pharmacovigilance has always aimed to help clinicians and patients make wiser therapeutical decisions as Dra. Marie Lindquist's once said. Therefore, we have developed at the Instituto Nacional de Cardiología Ignacio Chavez the Pharmacovigilance Institutional Center, establishing as our goals to manage a pharmacovigilance's system that aims to take the World Health Organization Challenge Medication Without Harm by promoting the rational use of medication, and identifying risks related to drugs before they impact the patients.
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This study was conducted to evaluate the impact of genetic polymorphisms on lipid profiles of statin users.
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The estimate for each year of the triennium 2020-2022 that will occur 30 thousand lung cancer new cases in Brazil1, which can be classified as: small cell lung cancer (SCLC) and non-small cell lung cancer cells (NSCLC), that corresponds the 85% of the cases2. The main NSCLC treatments are platinum-derived chemotherapeutics, highlighting carboplatin and paclitaxel3, adverse drug reaction (ADRs) may compromise the treatment. ABCC2 gene is involved in molecules of transport, polymorphs in this gene may be related wit ADRs and response compromising the effectiveness of treatment4.
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In this study, we investigated the association between ABCC2 polymorphism and clopidogrel response as well as the associated hypothetical mechanism.
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Paediatric oncology patients who develop severe chemotherapy-induced toxicity that requires dose reduction, delay or termination of treatment are at risk of decreased treatment efficacy. Previous research has provided evidence that genetic variants in TPMT, NUDT15, UGT1A1 and DPYD are associated with toxicity of anticancer drugs. This led to pharmacogenetic guidelines that are integrated into clinical practice in paediatric oncology. Recently, novel genetic variants have been associated with a higher risk of developing chemotherapy-induced toxicity. In this case series, we selected 21 novel variants and genotyped these in nine patients with excessive chemotherapy-induced toxicity using whole exome sequencing or micro-array data. We observed that six out of nine patients carried at least one variant that, according to recent studies, potentially increased the risk of developing methotrexate- or vincristine-induced toxicity. As patient-derived genetic data are becoming widely accessible in paediatric oncology, these variants could potentially enter clinical practice to mitigate chemotherapy-induced toxicity.
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Platinum-based agents, including cisplatin, carboplatin, and oxaliplatin, are indispensable for the treatment of lung cancer. The development of toxicity frequently …
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The emphasis is on genetic factors affecting idiosyncratic adverse drug reactions. These are generally rare and involve only a limited contribution from drug concentration. Genes …
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… However, ABCC2 rs717620 had meaningful influence on treatment outcomes. This … smokers carrying A-allele of ABCC2 rs717620 are more sensitive to platinum therapy [125]. …
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Antioxidants are molecules characterized by function rather than common structural motifs. Their common feature is the capability of acting “anti”-oxidants in biological systems. Owing …
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… Аллель Т (rs717620) в разных исследованиях связан как с повышенным, так и со сниженным клиренсом МТХ, в других работах не показано данной взаимосвязи. Аналогичная …
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В данной статье представлен обзор существующей литературы по фармакогенетическим детерминантам воздействия и токсичности антиретровирусных препаратов, а …
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The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. …
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Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is …
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The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous …
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Mycophenolate mofetil, an ester prodrug of mycophenolic acid (MPA), is widely used to prevent graft rejection after kidney transplantation. The …
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In the most recent decades, oxaliplatin has been used as a chemotherapeutic agent for colorectal cancer and other malignancies as well. Oxaliplatin interferes with tumor growth …
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… It was found that those who carrying C allele at rs717620 locus of the ABCC2 gene had a … They then tested 14 SNPs of 5 transporter genes, and found C allele at rs717620 locus and A …
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… Otherwise, no significant relationship with ABCC2 rs717620 and the incidence and severity of VIPN was observed in Arab children with ALL [Citation53]. …
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… Nevertheless, the rs717620 polymorphism in ABCC2 was found to affect the risk of diclofenac hepatotoxicity with increased risk in T allele carriers [Citation30]. The functional effect of …
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Delayed excretion of methotrexate can lead to life‐threatening toxicity that may result in treatment cessation, irreversible organ damage, and death. Various factors have …
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… In addition, polymorphisms in the ABCC family have previously been associated with proximal kidney tubule cell dysfunction, including ABCC2 rs717620, ABCC4 rs3742106, ABCC10 …
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Susceptibility to Chronic Myeloid Leukemia (CML) may be modulated by genetic variables. However, the majority of previous investigations have focused on genetically …
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Tacrolimus (Tac) is an effective remission inducer of refractory ulcerative colitis (UC). Gene polymorphisms result in interindividual variability in Tac pharmacokinetics. In this study, we …
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Carbamazepine can cause hypersensitivity reactions in ~10% of patients. An immunogenic effect can be produced by the electrophilic 10,11‐epoxide metabolite but not by …
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The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. …
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… 24C>T (5′UTR, rs717620) polymorphism was a risk factor for resistance to therapy in epileptic patients [124]. Indeed, nonsynonymous polymorphism c.1249G>A was associated with …
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What is known and objective MTX pharmacology and toxicity involve several metabolizing enzymes and transporters whose functions have been suggested to be altered by genetic …
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… Аллель Т (rs717620) в разных исследованиях связан как с повышенным, так и со сниженным клиренсом МТХ, в других работах не показано данной взаимосвязи. Аналогичная …
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What is known and objective Tacrolimus (FK506), an effective and potent calcineurin inhibitor, is the cornerstone of immunosuppression after kidney transplantation. Wuzhi capsule (…
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Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) …
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Osteosarcoma (OS) is one of the aggressive bone tumours commonly diagnosed in adolescents and young adults. Aim: The study aimed to investigate the effect of 9 single …
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… We therefore evaluated the association of plasma CP-1 concentration with the following SNPs: rs717620 (ABCC2 variant; cC-24T and 5′UTR), 33 rs12422149 (SLCO2B1 variant; c.…
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The aim of this study was to evaluate the impact of genetic polymorphisms in the pharmacokinetics of metabolism and transportation of lenvatinib in the Chinese population. Sixty-three …
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Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines …
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Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) …
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This study aims to evaluate the association between polymorphisms of methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity in Chinese patients …
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Introduction: HAART-associated metabolic syndromes have been reported, without such risk and genetic markers in patients with pre-existing heart failure (HF) being addressed. …
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… A significant association of ABCC2 rs717620 polymorphism with antiepileptic drug resistance … Research suggests that ABCC2 rs717620 and rs3740066 are risk factors that predict a …
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… The ABCC2 (rs717620) polymorphism is located in the promoter region of the gene, and has been previously associated with decreased protein expression in vitro [86]; …
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… We also show that variants in the genes for methotrexate transporters OATP1B1 (rs2306283/rs4149056 SLCO1B1 haplotypes) and ABCC2 (rs717620) are associated with increased …
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Background Tacrolimus is a key drug in kidney transplantation with a narrow therapeutic index. However, whether tacrolimus exposure variability affects clinical outcomes and adverse …
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Mycophenolic acid exhibits significant interpatient pharmacokinetic variability attributed to factors including race, sex, concurrent medications, and enterohepatic circulation of the …
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… carriers of the variant ABCC2 rs717620 allele or patients with SLCO1B1 … We identified the ABCC2 rs717620 genotype as a … ABCC2 rs717620 genotype is thus the first pharmacogenetic …
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Background Context: Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). MTX treatment is commonly associated with nausea. Large inter-individual …
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Methotrexate is an antimetabolite used in chemotherapy for acute lymphoblastic leukemia in underage patients, whose mechanism of action is the inhibition of DNA and RNA, …
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Background Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD …
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… Here, we identified the ABCC2 rs717620 genotype as a determinant of methotrexate drug … The common polymorphism rs717620 has been associated with reduced transporter activity…
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… For CsA Cssmin/D of oral administration, except for ABCC2 rs717620 and ABCG2 rs2231142 genotype, Cssmin/D of patients with ABCC2 rs717620 CC/CT genotype was significantly …
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… We found that ABCC2 rs717620, located on the gene promoter region, may be related to CRT survival in HNC patients. Patients carrying the minor allele (A) allele in the ABCC2 …
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Acute lymphoblastic leukaemia is the most prevalent cancer in children under 14 years of age in Malaysia, with an incidence rate of approximately 35 per one million children. Several potential environmental and lifestyle factors associated with the risk of childhood leukaemia have been investigated, such as infections, pesticides, traffic air pollution, industrial pollutant, diet, parental occupation and smoking habit. The study aimed to determine relationships between two SNPs; rs10821936 (ARID5B) and rs25487 (XRCC1), and risk associated in childhood ALL, as well as four SNPs; rs717620 (ABCC2), rs4948496 (ARID5B), rs1801133 (MTHFR) and rs4149056 (SLCO1B1), with the serum levels and toxicity of MTX. The study also sought to investigate the metabolic alterations associated with MTX and to determine the potential metabolic markers and pathway for drug responses. Genomic DNA was isolated from blood, and the polymerase chain reaction analysis was performed for the genotyping study. The variants were then annotated and analysed utilising Variant Effect Predictor (VEP), Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping version 2 (PolyPhen-2). In addition, the Agilent 1200 Infinity HPLC system coupled with the Agilent 6460 triple-quadrupole (QQQ) and Agilent 6520 Accurate-Mass (Q-TOF) mass spectrometers were employed to measure serum concentrations of MTX and to identify the potential metabolic markers, respectively. Eighty-one per cent of the patients have genotypes CC and CT of rs10821936 (ARID5B) were associated with 2.5 – 2.1 increase in the risk of developing ALL. The rs717620 ABCC2 genotype was significantly associated with MTX serum levels at 48 hours post-treatment (p = 0.017, Kruskal-Wallis Test). Patients with CT and TT of rs717620 (ABCC2) and TC and CC of rs4948496 (ARID5B) were significantly associated with grade I – IV leukopenia (Fisher Exact Test; p = 0.03 and 0.02, respectively). The metabolomics study found that thirteen metabolites significantly discriminated the pre- and post-MTX group. Out of the thirteen metabolites identified, the four metabolites with VIP scores of more than 1 were xanthine, alpha-linolenic acid, (9Z)-hexadecenoic acid and cholic acid. The findings revealed that xanthine was the most significant metabolic marker in childhood ALL with an AUC value of 0.88 (95%, CI = 0.84 – 0.92). Our results demonstrate that by pre-screening of ALL patients would identify whose patients at risk and therefore help a paediatric oncologist to personalize chemotherapy drugs for precision health.
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Hyperbilirubinemia is a predictor of severe drug-induced liver injury (DILI). Hepatobiliary ATP-binding cassette (ABC) transporters play an important role in the transportation of many drugs and bilirubin; however, little is known about these transporters and the risk of DILI. The aim of this study was to explore associations between genetic variations in important ABC transporters and susceptibility to DILI, with a particular focus on hyperbilirubinemia. Methods A total of 200 patients with DILI and 200 healthy controls were enrolled as the training dataset. Another 106 patients with DILI were recruited as the validation dataset. They were genotyped for ABCB11 (BSEP) rs2287622, ABCB1 (MDR1) rs1128503, rs1045642, ABCB4 (MDR3) rs2230028, ABCC2 (MRP2) rs1885301, rs717620, rs2273697, rs3740066 and rs8187710 using polymerase chain reaction-based TaqMan genotyping assays. Results There were no statistical differences in any of the nine ABC transporter single nucleotide polymorphisms between the DILI and control groups. However, in the DILI group, the patients with hyperbilirubinemia had a higher frequency of the ABCC2 rs717620 C/T and T/T genotypes than those without hyperbilirubinemia (44.2% vs 20.2%, p = 0.001). After adjusting for other confounding factors, the ABCC2 rs717620 T variant was still associated with an increased risk of hyperbilirubinemia (adjusted odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.73-8.48, p = 0.001). This association was confirmed by the validation dataset (adjusted OR: 3.92, 95% CI: 1.42-10.81, p = 0.015). We also found that the mortality group had higher frequencies of the ABCC2 (MRP2) rs717620 C/T and T/T genotypes than the survival group (50.0% vs 27.9%, p = 0.048). Conclusion Carriage of the ABCC2 (MRP2) rs717620 T variant may increase the risk of hyperbilirubinemia and mortality in patients with DILI. Screening for this variant may help to prevent and mitigate drug-induced hyperbilirubinemia.
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Accumulating evidence indicates that genetic polymorphisms in ATP-binding cassette superfamily members, such asABCC2 and ABCG2, alter responses to antiepileptic drugs (AEDs); however, this evidence is controversial and inconclusive. To provide strong evidence of the association between common polymorphisms in ABCC2 and ABCG2 and AED responses in patients with epilepsy, we performed a systematic review and meta-analysis. Methods A literature search of electronic databases (PubMed, EBSCO, Ovid and the China National Knowledge Infrastructure) was performed. To evaluate the association of genetic polymorphisms inABCC2 and ABCG2 and risk of AED treatment, we calculated pooled odds ratios (ORs) and 95 % confidence intervals (CIs) using a fixed- or random-effect model. Results A significant association of theABCC2 rs717620 polymorphism with resistance to AEDs was found in the overall pooled populations (homozygous comparison: OR = 1.77, 95 % CI, 1.27–2.48; dominant model: OR = 1.23, 95 % CI, 1.06–1.43; recessive model: OR = 1.75, 95 % CI, 1.28–2.40) and Asians (dominant model: OR = 1.21, 95 % CI, 1.03–1.42; recessive model: OR = 1.80, 95 % CI, 1.30–2.50). Using a recessive model, a similarly significant association of ABCC2 rs3740066 with AED resistance was observed in the overall pooled populations (OR = 2.29, 95 % CI, 1.44–3.64) and Asians (OR = 2.53, 95 % CI, 1.56–4.08). However, ABCC2 rs2273697, ABCG2 rs2231137 and rs2231142 were not found to be associated with AED responsiveness. Conclusion This meta-analysis suggests thatABCC2 rs717620 and rs3740066 are risk factors that predict responses to AEDs in epileptic patients.
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The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.
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Objective: to identify new single-nucleotide polymorphisms (SNPs) in genes encoding proteins involved in methotrexate (MTX) metabolism and to evaluate the associations of these SNPs with MTX toxicity or intolerance in a southern Spanish cohort of patients with rheumatoid arthritis (RA). Methods: An observational, retrospective, and multicenter study was conducted at three participating hospitals in southern Spain. The main variable was intolerance to MTX (i.e., bDMARD monotherapy), defined as an interruption of treatment due to adverse events or toxicity. Patients being treated with MTX and bDMARDs (combined treatment) at the time of the study visit were considered “tolerant” of MTX. Ten polymorphisms were selected for sequencing in our patients according to a literature review. Each polymorphism was classified according to three possible genotypes (e.g., two homozygous (AA or GG) and one heterozygous (AG)), and the association of these combinations with MTX intolerance was evaluated. Results: A total of 227 patients were included in the final analysis (107 intolerant of MTX and 120 tolerant). A significant association was observed between MTX intolerance and the GGH-T401C AA/AG genotype (OR 2.13, 95% CI 1.06–4.29) in comparison with the GG genotype. On the other hand, an inverse association was observed between the ABCC2-C24T TT/TC genotype and intolerance to MTX (OR 0.59, 95% CI 0.35–1.00) in comparison with the CC genotype. Conclusion: This study provides new data on the association between genetic polymorphisms and MTX intolerance, which may contribute to the development of new biomarkers and personalized medicine in patients with RA.
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Breast cancer (BC) is known as the most common malignancy in women. Environmental and genetic factors are associated with BC progression. Genetic polymorphisms have been reported as important risk factors of BC prognosis and drug response. Main body: Therefore, in the present review, we have summarized all single nucleotide polymorphisms (SNPs) which have been significantly associated with drug response in BC patients around the world. We have also categorized the reported SNPs based on their related genes functions to clarify the molecular biology of drug responses in BC.
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Genetic variants in genes involved in the distribution, metabolism, accumulation or repair of lesions are likely to influence the response of drugs used in the treatment of Head and Neck Cancer (HNC). We examine the effect of 36 SNPs on clinical outcomes in patients with locally advanced HNC who were receiving platinum-based chemoradiotherapy (CRT). These SNPs were genotyped in 110 patients using the iPLEX Gold assay on the MassARRAY method in blood DNA samples and used Kaplan–Meier and Cox regression analyses to compare genotype groups with the survival. Two SNPs, rs717620 (ABCC2) and rs12934241 (MMP2) were strongly associated with overall survival (OS) and disease-free survival (DFS). At a median follow-up of 64.4 months, the allele A of rs717620 (ABCC2) had an increased risk of disease progression {hazard ratio [HR] = 1.79, p = 0.0018} and death (HR = 2.0, p = 0.00027). ABCC2 was associated with OS after a Bonferroni adjustment for multiple testing. The MMP2 rs12934241‐T allele was associated with an increased risk of worse OS and DFS (p = 0.0098 and p = 0.0015, respectively). One SNP of ABCB1 and three SNPs located in the ERCC2 gene showed an association with response in the subgroup of HNC patients treated with definitive CRT. Our findings highlight the potential usefulness of SNPs in different genes involved in drug metabolism and repair DNA to predict the response and survival to CRT. ABCC2 is a potential predictor of OS in patients with HNC.
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Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3-4 toxicity. METHODS Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. RESULTS Reported grade ≤ 2 and 3-4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70-10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19-1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. CONCLUSION Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.
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In this review, we have summarized the pharmacokinetics, pharmacodynamics and adverse effects of imatinib, dasatinib, nilotinib, bosutinib, ponatinib and radotinib with focus …
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… The polymorphism rs717620 (ABCC2) affects the response of antiepileptic drugs [Citation23], influences the metabolism of erythromycin [Citation24] and is associated with toxicity …
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Acute lymphoblastic leukemia (ALL) is the leading cause of death from pediatric cancer worldwide. However, marked ethnic disparities are found in the treatment of childhood ALL with …
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… The rare polymorphism, rs9349256 has the lowest MAF of 0.01 while the common polymorphism, rs717620 has the highest MAF of 0.42, the average MAF being 0.19. In addition, a …
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Tamoxifen and its metabolites compete with estrogen to occupy the estrogen receptor. The conventional dose of adjuvant tamoxifen overwhelms estrogen in this …
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Mycophenolate mofetil is widely used in kidney transplant recipients. Mycophenolate mofetil is hydrolysed by blood esterases to mycophenolic acid (MPA), …
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… There is also an association of MTHFR rs1801133 and ABCC2 rs717620 with susceptibility to generalized tonic-clonic epilepsy, while ABCB1 rs717620 is associated with poor …
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El tratamiento estándar de primera línea en pacientes con cáncer gástrico consiste en regímenes de quimioterapias combinadas, en donde se incluyen generalmente …
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Mycophenolic acid (MPA) is an effective oral immunosuppressive drug used to treat lupus nephritis (LN), which exhibits large pharmacokinetic variability. This study aimed …
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To investigate how variability in multiple pharmacokinetic genes associates with telmisartan exposure, we determined telmisartan single‐dose (40 mg) pharmacokinetics and …
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Colorectal (CRC) and gastric (GC) cancers are associated with increased morbidity and mortality. Single nucleotide polymorphisms (SNPs) of xenobiotic metabolism and transporter …
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… Las más frecuentemente descritas son –24C>T (rs717620), 1249G>A (rs2273697) y 3972C>T (rs3740066), de las cuales rs717620 se ha relacionado con una expresión reducida de …
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Background Lamotrigine is an antiseizure drug (ASD) which was approved by the US Food and Drug Administration in 1994 to treat focal (partial) seizures, primary generalized tonic–…
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… (SNP) of ABCB1 gene C3435T (rs1045642) was first confirmed to be associated with epileptic drug resistance in a Caucasian population, several other SNP loci such as rs717620 of …
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Modern epidemiologic studies permit investigation of the complex pathways that mediate effects of social, behavioral, and molecular factors on health outcomes. Conventional analytical …
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NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir …
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… Citation29 A polymorphism in ABCC2 (rs717620) resulting from an alteration of C to T is known to be related to neoadjuvant chemotherapy’s pathological response. Another study has …
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… Citation16 Similarly, ATP-binding cassette subfamily C member 2 (ABCC2) −24C>T polymorphism (rs717620) contributed to variability in MTX kinetics, increasing its plasma …
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Objectives To assess associations between polymorphisms within genes encoding proximal tubule transporters implicated in tenofovir renal clearance and kidney tubular dysfunction (…
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Membrane transporters are the very crucial protein which transport endo and exogenous compound across the organelle and cellular membrane. These transportation make feasible …
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… C>T (rs717620) was significantly associated with the pharmacokinetics of deferasirox in the … C>T (rs717620) single-nucleotide polymorphism on deferasirox pharmacokinetics after a …
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Purpose A patient was denoted to be generic brittle (GB) if they had a negative opinion about generics (eg prior history of a switch problem) or took the innovator brand of their most …
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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of …
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Uvod in namen dela: Cilj zdravljenja epilepsije je popolna kontrola napadov in omejitev pojava neželenih učinkov, kar je pri otrocih in mladostnikih, kjer je zdravljenje s protiepileptičnimi zdravili večinoma dolgotrajno, še posebno pomembno. Genetske variante v genih, ki sodelujejo v presnovi in transportu protiepileptičnih zdravil, pomembno vplivajo na učinkovitost zdravljenja epilepsije in pojavljanje neželenih učinkov. V doktorski nalogi smo opredelili tiste genetske označevalce pri otrocih in mladostnikih z epilepsijo, ki vplivajo na učinkovitost zdravljenja s tremi pogosteje uporabljenimi zdravili in na pojav neželenih učinkov. Metode: Vključeno je bilo 165 otrok in mladostnikov z epilepsijo, ki se zdravijo na Kliničnem oddelku za otroško, mladostniško in razvojno nevrologijo Pediatrične klinike Univerzitetnega kliničnega centra v Ljubljani. Pridobili smo klinične podatke ter smo preiskovancem, z molekularno genetskimi preiskavami, določili izbrane polimorfizme v genih CYP3A4, CYP2C9, CYP2C19, ABCB1, ABCC2, ABCG2 in SCN1A. S statistično analizo s programom SPSS smo preverili povezave genetskih in kliničnih podatkov. Vključili smo tudi 95 zdravih kontrolnih preiskovancev. Raziskavo je odobrila Komisija za medicinsko etiko. Rezultati in razprava: Pri bolnikih zdravljenih z valproatom in genotipom TT polimorfizma ABCB1 rs1128503 se 4-krat pogosteje pojavlja neželeni učinek kognitivnih motenj v primerjavi z genotipom CT. Ta povezava v literaturi še ni bila opisana. Pri bolnikih z genotipom AG polimorfizma ABCC2 rs2273697 se 3-krat pogosteje pojavlja neželeni učinek kognitivnih motenj v primerjavi z genotipom GG, kar je v skladu z znanimi podatki o tem da je koncentracija valproata pri bolnikih z genotipom AA višja kot pri bolnikih z genotipom GG. Pri bolnikih z genotipom GG polimorfizma CYP2C19 rs4244285 se 2, 6-krat pogosteje pojavljajo vedenjske težave kot neželeni učinek v primerjavi z genotipom AA, medtem ko se za genotip AA 2, 8-krat pogosteje pojavljajo vedenjske težave kot neželeni učinek v primerjavi s kognitivnimi motnjami. Ta varianta je že bila povezana s pojavom drugih neželenih učinkov, kot sta porast telesne teže in hiperinzulinizem pri bolnicah z epilepsijo, ki so bile zdravljenje z valproatom, ni pa bila opisana v povezavi z vedenjskimi težavami. Pri bolnikih zdravljenih s karbamazepinom oz. okskarbazepinom in genotipom AG polimorfizma ABCC2 rs717620 se 3-krat pogosteje pojavljajo vedenjske težave kot neželeni učinek v primerjavi z genotipom GG, kar še ni bilo opisano v literaturi. Prvič smo dokazali, da je alel G polimorfizma SCN1A rs2298771, predvsem v homozigotni obliki, povezan z večjo učinkovitostjo protiepileptičnega zdravljenja. Hkrati je ta alel povezan tudi z dovzetnostjo za epilepsijo, ki je že bila opisana v azijskih populacijah. Zaključki: Rezultati naše in podobnih raziskav bodo lahko v prihodnosti osnova za določitev priporočil za individualizirano izbiro najprimernejšega protiepileptičnega zdravila, ki bo učinkovitejše in bo imelo čim manjšo možnost pojava neželenih učinkov zdravljenja.
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Osteosarcoma (OS) is one of the aggressive bone tumors commonly diagnosed in adolescents and young adults. The study investigated the effect of 9 single nucleotide polymorphisms (SNPs) in 5 genes on methotrexate (MTX) plasma level and its impact on the patients’ clinical outcomes.
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Osteosarcoma (OS) is one of the aggressive bone tumors commonly diagnosed in adolescents and young adults. The study investigated the effect of 9 single nucleotide polymorphisms (SNPs) in 5 genes on methotrexate (MTX) plasma level and its impact on the patients’ clinical outcomes.
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A patient was denoted to be generic brittle (GB) if they had a negative opinion about generics (e.g. prior history of a switch problem) or took the innovator brand of their most problematic anti-epileptic drug (AED) when generic was available. The aim of this hypothesis-generating study was to assess possible genetic and physiologic differences between GB and not GB patients with epilepsy.
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Studies had shown that genetic polymorphism plays a significant role in the pharmacokinetics and pharmacodynamics variation of high dose methotrexate (MTX), 5000 mg/m2 regimen. The objective of thi...
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Individuals receiving treatment with anti-tuberculosis (TB) drugs may experience serious side-effects, such as anti-TB drug-induced hepatotoxicity (ATDH). Genetic variants, …
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Hepatic transporters mediate the movement of substrates including medications and endogenous compounds (eg, bile acids) across membranes. Transporters are important …
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… Recent genetic study reported that several polymorphisms in the ABCC2 gene (rs3740067, rs3740073 and rs717620) significantly associate with OS of PDAC patients in an early …
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Acute hepatitis A virus (AHAV) infection is a self-limited condition that usually spontaneously recovers in 2–8 weeks. While in children under 6 years of age AHAV is often asymptomatic,…
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Tenofovir-associated renal toxicity is influenced by several factors, including plasma exposure and genetic variants in transporter-encoding genes. Tenofovir plasma exposure has been …
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Cisplatin-induced ototoxicity is a common permanent consequence of curative chemoradiation for locally advanced head and neck squamous cell carcinoma (HNSCC). …
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Hepatitis C virus (HCV) infection is an extensive health problem, which leads to serious liver diseases. Host genetic polymorphisms were associated with HCV infection, …
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The objective of this study was to merge genetic and non-genetic factors of tacrolimus pharmacokinetics to establish a more stable population pharmacokinetic model for …
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This study aimed to identify single-nucleotide polymorphisms (SNPs) that are associated with outcome to treatment with sunitinib in patients with advanced gastrointestinal stromal …
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… ) for the promoter variant rs717620 in the ABCC2 gene (… suggested that the ABCC2 rs717620-TT polymorphic genotype … , indicated that the ABCC2 rs717620-CC genotype was …
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Membrane transporters play an essential role in the pharmacokinetics of drugs as they mediate exchanges between biological compartments. Tacrolimus is characterized by wide …
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… The homozygous carriage of the G major allele (rs717620) is associated with a reduced protein function, the homozygous carriage of the minor A allele is associated with an increase in …
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… Besides, Zgheib and colleagues found that the ABCC2 rs717620 variant carriers needed a significantly longer time to reach a MTX level below 0.1 µmol/L during the consolidation …
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… rs717620 and female gender were associated with decreased response to simvastatin treatment in Chinese Han population.44 However, another study showed that ABCC2 rs717620 …
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Background Artisanal small-scale gold miners have high levels of mercury in human specimens often above recommended threshold values. There are differences reported in the …
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Background Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug toxicity may improve the success of the …
278
… Kaplan-Meier survival outcome analysis revealed a significant major overall survival (OS) for GG carriers of rs717620. The group of patients carrying the ABCC2 AG + AA genotype had …
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… The homozygous carriage of the G major allele (rs717620) is associated with a reduced protein function, the homozygous carriage of the minor A allele is associated with an increase in …
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Genetic polymorphisms are related to the concentration and efficacy of oxcarbazepine (OXC). 10-Hydroxycarbazepine (MHD) is the major pharmacologically active metabolite of OXC, and it exerts an antiepileptic effect. This study aimed to explore the connection between the MHD concentration and genes such as ATP-binding cassette B1 (ABCB1), ATP-binding cassette C2 (ABCC2), UDP-glucuronosyltransferase-2B7 and sodium voltage-gated channel alpha subunit 2 (SCN2A), which participate in the antiepileptic function of OXC.
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JI sl/en AI Tramadol je centralno delujoč opioidni analgetik za lajšanje akutnih in kroničnih bolečin. Encimi CYP2D6, UGT2B7, ABCB1 in ABCC2 so ključni za presnovo in transport tramadola. Polimorfizmi v genih za te encime bi lahko vplivali na farmakokinetiko tramadola in s tem na odgovor na zdravljenje. Namen raziskave je bil preveriti pogostnost teh polimorfizmov in njihov vpliv na odgovor na zdravljenje pri bolnicah po operaciji raka dojke. Preverili smo hipotezi, da je pogostost neželenih učinkov pri slabih presnavljalkah CYP2D6 manjša kot pri hitrih ali ultrahitrih presnavljalkah in da imajo nosilke polimorfizmov ABCB1, ABCC2 in UGT2B7 večje tveganje za pojav neželenih učinkov kot preiskovanke brez polimorfnih alelov. Pri 113 preiskovankah smo s kvantitativnim PCR določili frekvence alelov CYP2D6:* 3,* 4,* 5,* 6,* 10,* 41 in* 2xN, ABCB1 rs1128503, rs2032582 in rs1045642, ABCC2 rs2804402, rs717620 in rs2273697 in UGT2B7 rs7668258 in rs7668258, ter s statistično analizo preverili njihov vpliv na prekinitev zdravljenja in pojav neželenih učinkov. Bolnice homozigotne za polimorfni alel UGT2B7 rs28365063 GG so statistično značilno pogosteje prekinile zdravljenje zaradi neželenih učinkov. Vmesne in hitre presnavljalke CYP2D6 so statistično značilno pogosteje poročale o zaprtju (P= 0,005). Vplivi ostalih preučevanih polimorfizmov na tveganje za prekinitev zdravljenja ali pojav neželenih učinkov niso bili statistično značilni.
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… Verder is ABCC2 rs717620 significant geassocieerd met het optreden van graad 3/4 febriele neutropenie (OR = 2,72, 95%-BI = 1,13-6,53, P = 0,025). Patiënten met het rs717620 T/T …
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Chronic myeloid leukemia (CML) is the excessive proliferation of granulocytic lineage cells of hematopoietic system, its main characteristic is the Philadelphia chromosome, which consists of the translocation of chromosomes 9 and 22, resulting in the expression of BCR-ABL with unregulated tyrosine kinase enzymatic activity. The CML main treatment is imatinib (IMB), a selective tyrosine kinase inhibitor. However, literature reports a failure of therapeutic response in 25% of patients during the treatment of CML, which may be associated with individual genetic variability. ABC family genes encode carrier proteins that mediate the transport of substances into cells, including drugs. Genetic polymorphisms that modify the functionality of proteins encoded by these genes are related to the resistance of various drugs used in clinical practice. So, investigating polymorphism in these gene may help elucidate the therapeutic failure of IMB.
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Oxaliplatin-induced peripheral neurotoxicity (OXPN) is a dose-limiting toxicity in colorectal cancer (CRC) patients. Single nucleotide polymorphisms (SNPs) in genes involved in drug transport may lead to higher intracellular oxaliplatin accumulation in the dorsal root ganglia and thus increased risk of OXPN. In this study, a panel of 5 SNPs, namely ABCC2 (-24C > T/rs717620 and c.4544 G > A/rs8187710), ABCG2 (c.421 C > A/rs2231142), ABCB1 (c.3435 C > T/rs1045642) and SLC31A1 (c.-36 + 2451 T > G/rs10981694), was evaluated to assess their association with grade 2-3 OXPN in metastatic CRC patients. SNPs were considered according to a dominant model (heterozygous + homozygous). Germline DNA was available from 120 patients who received oxaliplatin between 2010 and 2016. An external cohort of 80 patients was used to validate our results. At the univariable logistic analyses, there were no significant associations between SNPs and incidence of OXPN. Taking into account the strength of observed association between OXPN and the SNPs, a clinical risk score was developed as linear predictor from a multivariable logistic model including all the SNPs together. This score was significantly associated with grade 2-3 OXPN (p = 0.036), but the external calibration was not satisfactory due to relevant discrepancies between the two series. Our data suggest that the concomitant evaluation of multiple SNPs in oxaliplatin transporters is an exploratory strategy that may deserve further investigation for treatment customization in CRC patients.
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Epilepsy is one of the most common neurological diseases with unclear etiology where its genetic background and treatment regime still need further exploration. Objectives This study designed to evaluate the pharmacogenomics of MTHFR and ABCC2 genes, and their association with epilepsy susceptibility among Jordanian population. Methods A case-control study was conducted on Jordanian cohort of 296 epileptic patients and 299 healthy individuals. Custom platform array was used to genotype the genetic polymorphisms within MTHFR (rs1801133) and ABCC2 (rs717620, rs3740066, rs2273697) genes. Results This study revealed a significant genetic association of MTHFR rs1801133 polymorphism with susceptibility to generalized in general and generalized tonic-clonic epilepsy (GTCE)(p=0.018 and 0.01, respectively). Regarding ABCC2 gene, rs717620 was of linkage with generalized and GTCE subtypes (p=0.045 and 0.048, respectively), while rs717620 was associated with poor responder patients (p=0.036) with no linkage of the ABCC2 haplotypes. Conclusions MTHFR and ABCC2 polymorphisms showed an association with either epilepsy types in general or subtypes and treatment response among Jordanian population. This study also suggested that these gene polymorphisms have an important role in epilepsy development and drug effectiveness and could be of a great impact in the era of epilepsy diagnosis and treatment.
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Breast cancer pharmacogenetics is increasingly being explored due to chemotherapy resistance among certain classes of patients. The ATP binding cassette (ABC) transporter genes have been previously implicated in breast cancer progression and drug response. In the present study, single nucleotide polymorphisms (SNPs) from the ABCC1, ABCC2, ABCB1, and ABCG2 genes were screened in breast cancer patients and healthy volunteers from the Jordanian-Arab population. Only the ABCB1 SNPs showed a significant association with BC in Jordanian-Arab patients, and the ABCB1 SNP rs2032582 exhibited a strong genotypic association with BC. With regard to the clinical characteristics of BC, the ABCC2 SNPs rs2273697 and rs717620 were found to be significantly associated with age at breast cancer diagnosis and breastfeeding status, while the ABCB1 SNP rs1045642 was significantly associated with age at breast cancer diagnosis. In terms of pathological characteristics, the ABCC1 SNP rs35628 and the ABCB1 SNP rs2032582 were significantly associated with tumor size, the ABCC2 SNP rs2273697 was significantly associated with estrogen receptor status, and the ABCG2 SNP rs2231142 was significantly associated with axillary lymph node status. In this current study, we assume that significant genetic variants within the ABC superfamily may increase the risk of breast cancer among Jordanian women. Furthermore, these variants might be responsible for worse BC prognosis.
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The objective of the study was to investigate the pharmacokinetic drug-drug interactions between tacrolimus (TAC) and mycophenolate mofetil (MMF) in healthy Korean male volunteers…
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The WHO currently recommends tenofovir (TFV) disoproxil fumarate (TDF) or TFV alafenamide (TAF) as a preferred first-line antiretroviral therapy (ART) for the treatment and prevention …
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The objective of this study was to examine the association between tacrolimus concentration in oral fluids and in whole blood and to investigate the various factors that …
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… 24C>T (rs717620). This promoter variant is associated with lower expression levels of ABCC277 (Table S3). Several candidate gene studies have identified significant associations of …
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… ABCC2基 因涉及多个SNP 位点, 其中ABCC2 rs717620 被认 为与MMF 治疗的移植患儿最为 相关[ 19 ].有研究报 道在因胃肠道不良反应而暂停MMF 使用的心脏移 植儿童中,ABCC2 rs717620…
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Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is frequently used to prevent acute graft-versus-host disease (aGVHD) in patients receiving hematopoietic …
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Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The …
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Clinical vignette A 21-year old woman was admitted to hospital with a two-week history of painless jaundice, fatigue and anorexia having previously been fit and well. One month prior to …
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Tacrolimus (Tac, or FK506), a calcineurin inhibitor (CNI), is the first-line immunosuppressant which consists of the footstone as immunosuppressive regimens in kidney …
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… Each SNP, apart from rs717620, was associated with a decrease of eGFR with each minor allele. Evaluation of the raltegravir group identified no SNPs that were associated with eGFR. …
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Variability in genes implicated in drug pharmacokinetics or drug response can modulate treatment efficacy or predispose to adverse drug reactions. Besides common …
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The immunosuppressant mycophenolic acid (MPA), derived from the prodrug mycophenolate mofetil (MMF), is a drug used widely by kidney transplant recipients. This drug selectively …
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Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), …
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… [47] reported that patients with the CC genotype of − 24 C/T (rs717620) in the ABCC2 gene were at a significantly higher risk of skin rash than those with the CT genotype. Carriers of the …
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Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is used to suppress GvHD in patients undergoing hematopoietic stem cell transplantation (HCT). The purpose of …
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Membrane transporters can be major determinants of the pharmacokinetic profiles of anticancer drugs. The associations between genetic variations of ATP-binding cassette (ABC) and …
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Multidrug resistance protein 2 (MRP2), encoded by ABCC2, has a putative role in tacrolimus (TAC) disposition. Conflicting data exist regarding the association between …
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… These authors also showed that the polymorphism rs717620 ABCC2, another ABC efflux transporter, was associated with low methotrexate levels. However, the evidence for variant …
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Several factors contribute to the high variability of linezolid plasma exposure in patients. Very recently, it has been suggested that linezolid could be an ABCB1 substrate. …
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This study aimed to identify single-nucleotide polymorphisms (SNPs) that are associated with outcome to treatment with sunitinib in patients with advanced gastrointestinal stromal …
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Recent studies have suggested that genomic diversity may play a key role in different clinical outcomes, and the importance of SNPs is becoming increasingly clear. In this article, we …
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… The variant genotype (TT) of ABCC2 (rs717620) was associated with spina bifida (OR 5 5.4, 95%CI: 1.3–22.4). The heterozygous genotypes of ABCC2 (rs3740066), CYP2C9 (…
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… Also the CC rs717620 in ABCC2 gene was found to be related to longer PFS and efficacy of first-line FOLFIRI in advanced CRC patients [17]. In addition carriers of GT rs2032582 …
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To date, antiretroviral therapy is highly effective in HIV-affected patients, but the individualization of such a life-long therapy may be advised. This review briefly summarizes the main …
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Efecto de los polimorfismos en UGT, SLCO, ABCB y ABCC en la toxicidad del tratamiento con irinotecán
Antecedentes y objetivos Evaluar la relación entre la presencia de polimorfismos en los genes implicados en la farmacodinamia del irinotecán (UGT1A, SLCO1B1, ABCB1 y ABCC2) y …
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We evaluated the contribution of patient‐specific clinical and genetic factors to statin‐related muscle toxicity (SRM) without a significant creatine kinase elevation (125 cases related to …
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Objectives: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but nevertheless 30% of patients experience MTX inefficacy. Our aim was to develop a clinical …
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… It should also be mentioned that ABCC2 rs717620 has been shown to be important to … [Citation58], a Caucasian patient heterozygous for these variants in both ABCC2 rs717620 and …
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… Only the studies concerning rs717620 and rs2273697 of ABCC2 gene showed consistent results. The rs717620 T allele was found to be associated with increased MTX plasma …
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Purpose: Irinotecan is an anticancer medicine which is used mostly in metastatic colorectal cancer (mCRC) treatment as second or third line chemotherapy. Several factors affect its …
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Background and objectives Evaluate the relationship between the presence of polymorphisms in genes involved in the pharmacodynamics of irinotecan (UGT1A, SLCO1B1, ABCB1 …
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… The variant rs717620 is located in the 5′-UTR of the gene and has been related to the pharmacokinetics of methotrexate, cyclosporine mycophenolic acid and efavirenz [Citation52–55]…
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… rs717620 genotype on ABCC2 expression 39,43 . We found that ABCC2 mRNA expression levels in breast tissue did not significantly differ with respect to rs717620 … ABCC2 rs717620 …
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… CC at position 24 of the ABBC2 (MRP2, rs717620) gene. In multivariate analysis, genotype CC at … Genotype CC at position 24 of the ABBC2 (MRP2 rs717620) gene was significantly …
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Background: Perioperative treatment is standard of care in Western Europe for locally advanced gastroesophageal cancer (GEC)[gastric and gastroesophageal junction (GEJ) …
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Objective The aim of this study was to evaluate the potential association between candidate genetic polymorphisms and vincristine-related peripheral neuropathy in Arab children with …
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… The aim of this study was to evaluate the association of rs717620 of … The ABCC2 SNP rs717620 was genotyped from blood … genetic effects of SNP rs717620 on the incidence of high- or …
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… rs717620 was 0.232. Overall, atorvastatin response was not associated with the ABCC2 rs717620 … TG/HDL-C ratio are affected by the rs717620 SNP in Chilean males but not female …
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Taxanes and anthracyclines are widely used in the treatment of breast cancer, although the benefit is limited to a proportion of patients and predictive biomarkers for clinical outcome remain elusive.
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Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases in childhood. Methotrexate (MTX) is recommended as an initial disease modifying anti-rheumatic drug (DMARD). When MTX is not effective or when intolerable adverse events (AEs) occur, biologic drugs are used. TNF alfa inhibitors are most commonly used biologic drugs in JIA. Early predictors are needed to identify patients who will not respond to a particular therapy or develop AEs. There is growing evidence that single nucleotide polymorphisms (SNPs) within the pathway genes are significant contributors to inter-individual differences in response to drugs.
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The aim of this study was to evaluate the potential association between candidate genetic polymorphisms and vincristine-related peripheral neuropathy in Arab children with acute lymphoblastic leukemia (ALL).
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To evaluate genetic variants affecting mycophenolic acid (MPA) metabolism in Chinese renal transplant recipients.
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To investigate the role of the ATP binding box C subfamily 2 transporter protein (ABCC2) gene in drug-resistant epilepsy.
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Imatinib mesylate is the drug of choice for patients with chronic myeloid leukemia (CML). Imatinib pharmacokinetics is affected by a number of transport proteins and enzymes. Material and methods In the present study we evaluated the association of eight polymorphisms in the seven genes CYP3A5*3 (rs776746), CYP3A4*1 (rs2740574), CYP2C9*3 (rs1057910), SLC22A1 (rs683369), ABCB1 (rs1045642, rs1128503), ABCG2 (rs2231142) and ABCC2 (rs717620) with imatinib plasma level and achieving an optimal clinical response in 112 CML patients (53 men and 59 women). Results No association was found between the examined polymorphisms in rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 and the achieved imatinib plasma level. The influence of rs776746 (CYP3A5*3) on the achievement of a complete cytogenetic response (CCyR) at 6 months was borderline non-significant (p = 0.06). Furthermore, no association was demonstrated between rs776746 polymorphisms and the achievement of a major molecular response (MMR) at 12 or 18 months. Polymorphisms rs776746, rs2740574, rs1057910, rs683369, rs1045642, rs1128503, rs2231142, rs717620 showed no impact on the optimal therapeutic response. Conclusions Despite the results of some other studies, no other polymorphism we analyzed was associated with imatinib plasma level or clinical response. The treatment outcomes cannot be predicted using the candidate gene approach and treatment decisions cannot be made according to the polymorphisms investigated in this study.
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Statin therapy reduces cardiovascular events in patients with, or at risk of, atherosclerotic cardiovascular disease. However, statins are underutilized in patients for whom they are indicated and are frequently discontinued. Discontinuation may be the result of statin-associated muscle symptoms (SAMS), which encompass a broad spectrum of clinical phenotypes from myalgia to severe myopathy. As with many adverse drug reactions (ADRs), inter-individual variability in susceptibility to SAMS is due, at least in part, to differences in host genetics. The genetic basis for SAMS has been investigated in candidate gene studies, genome-wide association studies, and, more recently, studies of multi-omic networks, including at the transcriptome level. In this article, we provide a systematic review of the pharmacogenetic basis of SAMS, focusing on how an understanding of the genetic and molecular determinants of SAMS can be considered in a personalized approach to reduce the incidence of this ADR, optimize statin adherence, and reduce the risk for cardiovascular events.
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… The Paediatric Heart Transplant Study, involving 290 patients, showed that rs717620 GG genotype was associated with increased rejection risk consistent with lower drug exposure [102…
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Antiretroviral therapy (ART) drugs have increasingly been shown to contribute significantly to the morbidity of HIV positive patients exposed to them. This is more so with increasing …
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Human exposure to mercury is still a major public health concern. In this context, children have a higher susceptibility to adverse neurological mercury effects, compared to adults with …
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Multidrug resistance protein-2 encoded by the ABCC2 gene (MRP2/ABCC2), an efflux transporter expressed at the proximal renal tubule, is rate-limiting for urine excretion …
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Since the identification of BRCA1 and BRCA2 a number of other genes have been reported to be associated with an increased risk of breast cancer. Many of these genes have now …
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… well-studied ABCB1 and ABCG2 efflux transporters, a single cross-sectional study in 62 Japanese CML patients found no significant ABCC2 (MRP2 efflux transporter) 24C>T (rs717620…
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… Patients with the TT diplotype at rs717620 in ABCC2 may experience increased clearance of erythromycin compared with patients with the CC and CT diplotypes 20 . …
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We searched our CHB and CHD databases for patients who had received treatment for CHB and CHD. 99 CHD patients (70M/29F; mean age: 40.0±10.6 years, 19 cirrhotic/80 …
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Complex oncologic patients require high standards of care, multidisciplinary approach and great resources. The aim of our study is to evaluate the capability of the 3M …
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… reported higher 48 h plasma concentrations (×1.6) in patients with the particular allele ABCC2 C24-T (rs717620). This was also associated by a higher risk of toxicity […
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… In the study on diclofenac DILI described above where an association with UGT2B7 polymorphisms was detected, carriage of an upstream polymorphism in ABCC2 (rs717620; −24C>T) …
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… In more detail, ABCC2-24C>T (rs717620) was correlated to kidney damage since the percentage of individuals with KDT was significantly higher among those with genotype CC than …
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Key Clinical Message This manuscript describes the case of a patient with sickle cell anemia who died of fulminant hepatitis after therapy with the iron chelator Deferasirox. The patient …
345
Associations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (eg, P-glycoprotein and MRP2) and different types of cancer have …
346
Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this …
347
Multidrug resistance (MDR) remains a substantial problem in chemotherapy. The purpose of the study was to investigate potential factors, including MDR genes polymorphisms, that …
348
The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in …
349
Imatinib 400 mg per day is first-line therapy for patients with gastrointestinal stromal tumours (GISTs). Although clinical benefit is high, progression-free survival (PFS) is …
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The study aims to evaluate the impact of recipients’ and donors’ polymorphisms in multidrug resistance-associated protein 2 (MRP2) gene ABCC2 -24C>T and 1249G>A on …
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… In addition to the rs3740066 variant, patients with the CT genotype for the rs717620 ABCC2 … Few patients were homozygous for the rs3740066 and rs717620 variants in ABCC2 and, in …
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Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug-toxicity may improve the success of the …
353
Several studies examined a possible link between multidrug resistance-associated protein 2 (ABCC2) gene variants and the risk of resistance to antiepileptic drugs (AEDs) in epilepsy, …
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… Three variants of ABCC2 (rs717620, rs3740066 [both analyzed in this study], and rs2273697) form haplotypes, which influence the transport capacity.25 ABCC2 haplotypes containing c…
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Background Sorafenib (Nexavar, BAY43-9006) is an oral anticancer drug approved by the US Food and Drug Administration (FDA) for the treatment of advanced renal cell carcinoma (…
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Introdução: A Leucemia Linfoblástica Aguda (LLA) é o câncer infantil mais comum em todo o mundo. Os fármacos 6-mercaptopurina (6-MP) e metotrexato (MTX) são medicamento-…
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… Genotyping for SNPs in MDR1 3435 rs1045642 C>T, 2677 rs2032582 G>T and 1236 rs1128503 C>T, MRP2 -24 rs717620 G>A and 1249 rs2273697 G>A, MRP4 *879 rs1059751 …
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Purpose: This study aimed to understand the effects of single nucleotide polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the pharmacokinetics (…
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… Our results indicated that gene polymorphism at the ABCC2 rs717620 locus was associated … relationship between the polymorphism at ABCC2 rs717620 and prognosis of patients with …
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To identify clinical and pharmacogenetic determinants of efficacy and toxicity of methotrexate (MTX) in juvenile idiopathic arthritis (JIA) over time.
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There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics in lupus nephritis (LN) patients on long-term maintenance immunosuppression. METHODS: Blood MPA level at 1, 2, 4, 8, 10 and 12 hours post-dose (i.e. C1, C2, C4, C8, C10 and C12) was measured in clinically stable LN patients receiving maintenance prednisolone and MMF, and repeated every 6 months. The relationship between MPA exposure and single nucleotide polymorphisms (SNP) related to the ATP Binding Subfamily C Member 2 (ABCC2) (rs2273697, rs3740066, rs717620 and rs17222723), organic anion transporting polypeptides (OATP) (rs7311358 and rs4149117) and uridine diphosphate glucuronosyltransferase (UGT) (rs17863762, rs6714486, rs17868320 and rs72551330) was investigated. RESULTS: Seventy-three LN patients receiving prednisolone (6.8±2.4 mg/D) and MMF (1151.5±501.7 mg/D) were included. C1, C2 and C12 MPA levels were 9.4±8.1 mg/L, 8.1±5.9 mg/L and 2.1±1.7 mg/L respectively, and all correlated with AUC0-12 (r= r=0.521, 0.852 and 0.765, p=0.004, <0.001 and <0.001 respectively). C12 level inversely correlated with hemoglobin, total immunoglobulin, IgG, IgA and IgM levels, and leukocyte and platelet counts (p<0.05, for all). Four episodes of disease flares occurred during 17.8±7.3 months of follow-up, giving a relapse rate of 1 in 320 patient-months. C12 MPA levels were similar between relapse and non-relapse patients (2.1±0.9 mg/L vs. 2.4±1.2 mg/L, p=0.738). Higher MPA C12 levels were associated with anaemia (2.9±1.5 mg/L and 1.7±1.1 mg/L in patients with haemoglobin below or >10 g/dL respectively, p=0.003). MPA exposure was not related to infection (n=2) or gastrointestinal upset (n=3). SNP rs2273697 G/G in the ABCC2 gene was associated with higher MPA exposure (1891.5±918.9 mghL-1/gkg-1 vs. 1075.9±239.9 mghL-1/gkg-1, p=0.003) and lower total lymphocyte count (1.6±0.8 vs. 2.1±0.2 109/mL, p=0.01) compared with A/G genotype. SNPs of OATP and UGT were not related to MPA exposure. CONCLUSIONS: C12 MPA level correlated with AUC0-12 and is related to haematological parameters and immunoglobulin suppression. SNP rs2273697 G/G genotype of the ABCC2 gene is associated with higher MPA exposure and lymphopenia.
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Tenofovir (TDF) is one of the most widely used antiretroviral drug. Despite the high degree of tolerability a small percentage of patients experienced alteration in tubular function during TDF use. Intracellular TDF disposition is regulated by ATP-binding cassette (ABC) drug efflux transporters and, a reduced transport activity may be implicated in accumulation of TDF into the cells. The aim of our study was to assess the major determinants of TDF associated tubular dysfunction (KTD) in a real-life setting including the usefulness of single-nucleotide polymorphisms (SNPs) mapping into ABCC2, ABCC4 and ABCC10 genes. We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from April 2013 to June 2016. All patients treated with TDF who underwent a genotypization for the functional variants mapping in ABCC2 rs717620 (−24 C > T), ABCC4 rs1751034 (3463 A > G) and ABCC10 rs2125739 (T > C) were evaluated. KTD was defined as the presence of urine phosphate wasting and/or proteinuria at 24 h urine analysis. One hundred fifty-eight patients were genotyped, of which 42 (26.6%) experienced signs of KTD. No statistical significant differences were observed among patients with or without KTD regarding age, gender, ethnicity and comorbidities (hypertension and diabetes). The percentage of patients with KTD was higher among those with “GG” genotype at rs1751034 of ABCC4 compared to patients without KTD [6 (14.3%) vs 4 (3.5%), p = 0.01]. No statistical significant differences were observed regarding the distribution of ABCC2 and ABCC10 SNPs. Carriers of “G” allele in homozygous status at rs1751034 of ABCC4 showed a significant association with KTD (Odds Ratio 4.67, 95% CI 1.25–17.46, p = 0.02) in bivariate analysis, but this association was lost in multivariable analysis. A significant association between bone diseases and KTD was observed (Odds Ratio 3.178, 95%CI 1.529–6.603, p = 0.002). According to our results ABCC4 rs1751034 could be a genetic determinant of KTD; however validation studies are needed for therapy personalization. Noteworthy, a strong association between bone disease and KTD was also observed.
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The ATP-binding cassette family transporter MRP2 (multidrug resistance-associated protein 2), encoded by the ABCC2 gene, is involved in the renal excretion of numerous xenobiotics and it is likely that it also transports many endogenous molecules arising from not only normal essential metabolic processes but also from environmental toxins or food intake. We used a targeted gas chromatography-mass spectrometry metabolomics analysis to study whether endogenous organic anions are differentially excreted in urines of healthy volunteers according to their genotype for three functional single nucleotide polymorphisms (SNPs) in ABCC2. This was the case for 35 of the 108 metabolites analyzed. Eight of them are most likely substrates of MRP2 since they are the most contributive to the difference between carriers of a decreasing function allele vs those carrying an increasing function one. Seven out of 8 metabolites are fatty acids (dodecanoic acid; 3-hydroxypropanoic acid) or metabolites of polyphenols (caffeine; resorcinol; caffeic acid; 2-(3,4-dihydroxyphenyl) acetic acid; and 4-hydroxyhippuric acid). Most of them were structurally similar to a series of substances previously shown to interact with MRP2 function in vitro. Interestingly, coproporphyrin isomer I, a prototypical substrate of MRP2, also belonged to our final list although it was not significantly discriminant on its own. This suggests that the simultaneous measurement of a set of endogenous metabolites in urine, rather than that of unique metabolites, has the potential to provide a phenotypic measure of MRP2 function in vivo. This would represent an innovative tool to study the variability of the transport activity of MRP2 under a physiological or pathological condition, especially in pharmacokinetic studies of its substrates.
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Aufgrund stetig neu entwickelter Arzneistoffe in den letzten Jahrzehnten ist es möglich geworden, immer mehr Erkrankungen mit Medikamenten zu behandeln. Leider wird in sehr …
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… -agent, the ABCC2 -24C>T rs717620 was associated with the variability of irinotecan plasma … It is worthwhile noting that the ABCC2 rs717620 and rs17222723 have been reported to be …
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Context Adefovir dipivoxil (ADV) was an important cause of adult-onset hypophosphatemic osteomalacia. However, its clinical characteristics and mechanisms have not been well …
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The individual response to targeted tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell cancer (mRCC) is highly variable. Outlined in this article are …
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… As but one of many unreplicated examples, carriers of one variation in the efflux transporter multidrug resistance protein 2 (MRP2) encoded by ABCC2 (rs717620) had a higher risk of …
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Single-nucleotide polymorphisms (SNPs) among drug-metabolizing enzymes and transporters (DMETs) influence the pharmacokinetic profile of drugs and exhibit intra- and interethnic …
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Efflux transporters like MDR1 and MRP2 may modulate the pharmacokinetics of about 50 % of all drugs. It is currently unknown how much of the variation in the activities of …
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This study aimed to identify associations between germline polymorphisms and risk of high-grade osteosarcoma (HGOS) development, event-free survival (EFS) and toxicity in HGOS …
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This study was performed to select single nucleotide polymorphisms (SNPs) related to the body burden of heavy metals in Koreans, to provide Korean allele frequencies of selected …
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Studies of genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are crucial to the development of therapeutics in clinical medicine. …
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Sorafenib-treated patients display a substantial variation in the incidence of toxicity. We aimed to investigate the association of genetic polymorphisms with observed toxicity on …
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Our aim in this chapter is to present the state of the art, including our own group research, in the field of immunosuppressant pharmacogenetics in the four main types of solid organ …
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The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are …
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… 24C>T (rs717620) was associated with increased plasma concentrations as well as an increased risk of clinical adverse drug reactions.The ABCC4 variant c.1372A>C (rs9516519) is …
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The pharmacogenetics and pharmacokinetics of efavirenz (EFV) have been widely studied, although data in the Italian population are limited. Single nucleotide polymorphisms (SNPs) …
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Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of …
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Background: Valproic acid (VPA) is a widely used antiepileptic drug with acceptable safety and efficacy in treating pediatric patients with various kinds of seizures. However, …
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Clinical resistance to chemotherapy is one of the major problems in breast cancer treatment. In this study we analyzed possible impact of 22 polymorphic variants on the treatment …
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… 24C>T (rs717620) variants with drug resistance in epilepsy [Citation22,Citation73–74]. Despite the fact that mutant alleles of these SNP are not as common as those of rs4148386 and …
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Background In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected …
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… parameters were associated with four SNPs of the ABCB1, ABCC3, NR1I2, and GGH genes, and toxicity was shown to be associated with ABCC1 rs246219 and ABCC2 rs717620 …
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Background ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. Aims To evaluate the association of …
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Introduction: Regular blood transfusions may result in hemochromatosis, leading to damage of various organs. Deferasirox exhibits good efficacy as iron chelation therapy, however …
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… In this study, we did not observe significant correlations between rs717620 variants and … In the same study, homozygosity for a reduced-function variant at rs717620 was also correlated …
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… In the present study, ABCC2 rs717620 was demonstrated to be associated … Furthermore, we found that the ABCC2 rs717620 … ABCC2 rs717620 had also been found to be moderately …
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Background: Oxaliplatin-based chemotherapy is a standard treatment for metastatic colorectal cancer (mCRC). Chronic peripheral neuropathy often limits its prolonged use in …
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… ABCC2 rs2273697 and rs717620 single nucleotide polymorphisms in … The TT genotype of the ABCB1 rs717620 polymorphism was … Thus, our study suggests that the ABCC2 rs717620 …
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The increase in life expectancy of patients with sickle cell disease (SCD) has led to the need for constant revisions of their clinical approach. Blood transfusions are part of the treatment of these patients and provide many benefits such as preventing and treating acute and chronic events; however, iron overload is a major complication [1–3]. The use of iron chelators especially in this group of patients may present some obstacles with quite deleterious effects [4–6]. The use of biological markers that could define groups at greater risk for these complications would help to define the best chelator for a particular patient [7].
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Several studies have evaluated the efficacy of neoadjuvant treatment using oxaliplatin and fluoropyrimidines in advanced gastric cancer (GC). However, preoperative biomarkers predictive of clinical outcome remain lacking. We examined polymorphisms in the MTHFR, DPYD, UMPS, ABCB1, ABCC2, GSTP1, ERCC1, and XRCC1 genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 103 GC patients treated with preoperative chemotherapy. DNA was extracted from peripheral blood cells, and the genotypes were analyzed using a SNaPShotTM assay, polymerase chain reaction amplification, and sequencing. The ABCC2-24C > T (rs717620) genotype was associated with pathologic response to neoadjuvant chemotherapy. Patients with the TT and TC genotypes responded to neoadjuvant chemotherapy 3.80 times more often than those with the CC genotype (95% CI: 1.27–11.32). Patients with the CC genotype also had poorer outcomes than those with other genotypes. Thus, ABCC2-24C > T polymorphism may help to predict the response to preoperative chemotherapy in GC patients.
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Platinum‑based chemotherapy is the first‑line treatment of non‑small cell lung cancer (NSCLC); it is therefore important to discover biomarkers that can be used to predict …
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Genetic factors have a significant impact on the PK variability of EFV, much higher than other non-genetic factors, such as demography. In this work we have performed a comprehensive PG analysis of genes encoding the major metabolizing enzymes and transporters of EFV, establishing a clear relationship between the PK parameters and genetic factors, which explain 50% of the variability in EFV PK parameters. The most relevant associations for metabolizing enzymes were found in CYP2B6 (rs3745274), in agreement with previous studies. The influence of transporters on the kinetics of EFV was also proved with significant correlations between the PK parameters of EFV and MRP4 (rs1751034, rs2274407). Analysis of gene-gene interactions with CYP2B6 was particularly useful to reinforce the role of MRP4 and to reveal unknown associations, such as that of DRD3. However, the role of DRD3 cannot be a direct effect but an indirect one due to physical proximity of NAT and the DRD3 locus in the genome.
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Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer (NSCLC); it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment. Four important transporter genes are expressed in the kidney, including organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), ATP-binding cassette subfamily B member 1 (ABCB1), and ATP-binding cassette subfamily C member 2 (ABCC2), and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs. This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinum-based chemotherapy response and toxicity in NSCLC patients. A total of 403 Chinese NSCLC patients were recruited for this study. All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy. The tumor response and toxicity were evaluated after two cycles of treatment, and the patients’ genomic DNA was extracted. Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.
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… The pharmacogenomics study of MMF in 59 pediatric HT patients has shown that ABCC2 rs717620 GG phenotype was protective against gastrointestinal side effects due to MMF. The …
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The co-administration of antiretroviral therapy (HAART) and anticancer drugs in oncologic patients HIV-positive, may be related with an increased risk of toxicity resulting to …
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Pharmacogenetic knowledge has already had considerable impact on antiretroviral prescribing. With continued advances in the field of human genomics, the impact of …
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… As a result, genotype C/C at -24 (rs717620) and genotype A/A at 1249 (rs2273697) on the ABCC2 gene, which encode MRP2, consistently shown the association with tenofovir-induced …
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… In patients with lung cancer, SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy, but strongly associated with shorter PFS and OS in SCLC, but …
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В настоящее время практически не изученным остается механизм регуляции экспрессии генов АВСтранспортеров, который связан с индивидуальными особенностями …
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Pemetrexed is a commonly used chemotherapeutic agent for lung adenocarcinoma patients. We investigated the impact of the genetic polymorphisms on the therapeutic efficacy of …
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To investigate whether single nucleotide polymorphisms (SNP) of drug transporter proteins for TDF is a risk factor for TDF-related renal function decrement. Methods This …
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Tenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded by ABCC2 and ABCC4, respectively. Genetic …
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Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment. Single nucleotide polymorphisms (SNPs) could be used as predictors of patients’ therapeutic …
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Determine the effect of the genetic variants beyond CYP3A5*3 on tacrolimus disposition. Patients & methods: We studied genetic correlates of tacrolimus trough concentrations …
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The authors wish to correct a mistake on the review “The role of drug transporters in the kidney: lessons from tenofovir” regarding the details of a particular ABCC2 polymorphism (–24C …
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… Studies have found that in some populations the specific single nucleotide polymorphism (SNP) in genes such ABCB1 rs1045642 for P-gp, ABCC2 rs717620 for MRP2 leading to …
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Individuals differ in susceptibility to mercury neurotoxicity, in part, due to underlying genetic differences. This review aims to evaluate the state-of-the-art of the effect of (1) genetics on …
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Tenofovir disoproxil fumarate (TDF) causes kidney toxicity in some patients. We carried out genomewide analyses to identify associations with plasma tenofovir clearance …
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AIM: To investigate the predictors of proximal kidney tubular dysfunction (PKTD) induced by adefovir dipivoxil (ADV) treatment for chronic hepatitis B. METHODS: Seventy-nine patients (…
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… In particular, ABCC2 rs717620 has been earlier associated with decreased protein expression in … In addition, ABCC2rs717620 and rs3740066 have had a combined effect in increasing …
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… In the present study we have evaluated the impact of ABCC2 rs717620, rs3740066 and rs2273697 upon blood MPA levels. Heterozygous patients (CT) at ABCC2 rs3740066 had …
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… rs717620位点基因型和等位基 因分布频率比较,差异有统计学意义(P<0.05).两组鳞癌患者 ABCC2基因rs717620… 两组ⅢB,Ⅳ期患者ABCC2基因rs717620位点基因型和等位基因分布频率比 较,…
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Patients with rheumatoid arthritis receiving methotrexate show different responses to treatment. Therefore, this study investigate whether changes in efficacy and toxicity were correlated …
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Objective This study evaluated the impact of seven single nucleotide polymorphisms in five candidate genes (ABCB1, ABCC2, ABCC4, SLC22A6, and SLC22A11) in relation to …
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Multidrug resistance proteins (MRP2, ABCC2) may play a role in drug resistance in epilepsy by limiting gastrointestinal absorption and brain access of antiepileptic drugs (AEDs). We sought to investigate the effects of ABCC2 polymorphisms on plasma carbamazepine (CBZ) concentrations and pharmacoresistance in Chinese patients with epilepsy. ABCC2 rs717620, rs2273697, rs3740066 polymorphisms were genotyped by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis or direct automated DNA sequencing in 80 patients treated with CBZ monotherapy. There were no differences in CBZ maintenance doses or adjusted plasma CBZ concentrations among the ABCC2 rs717620, rs2273697 and rs3740066 genotypic groups. No associations between all the studied genotypes and haplotypes involving the three SNPs of ABCC2 and CBZ resistance were observed in this patient cohort. These results suggest that ABCC2 polymorphisms may not contribute to interindividual variabilities in CBZ daily maintenance doses, plasma concentrations, and treatment efficacy.
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Multidrug resistance proteins (MRP2, ABCC2) may play a role in drug resistance in epilepsy by limiting gastrointestinal absorption and brain access of antiepileptic drugs (AEDs). We sought to investigate the effects of ABCC2 polymorphisms on plasma carbamazepine (CBZ) concentrations and pharmacoresistance in Chinese patients with epilepsy. ABCC2 rs717620, rs2273697, rs3740066 polymorphisms were genotyped by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis or direct automated DNA sequencing in 80 patients treated with CBZ monotherapy. There were no differences in CBZ maintenance doses or adjusted plasma CBZ concentrations among the ABCC2 rs717620, rs2273697 and rs3740066 genotypic groups. No associations between all the studied genotypes and haplotypes involving the three SNPs of ABCC2 and CBZ resistance were observed in this patient cohort. These results suggest that ABCC2 polymorphisms may not contribute to interindividual variabilities in CBZ daily maintenance doses, plasma concentrations, and treatment efficacy.
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Drug resistance is common in epilepsy despite multiple available medications. Single nucleotide polymorphisms (SNP) may influence drug efficacy in epilepsy. We therefore aimed to clarify the association between polymorphisms of several controversial SNP loci and drug resistance in Chinese Han epilepsy patients from central China. Among all the 391 recruited subjects, 235 and 156 patients were classified into a drug responsive and resistant group, respectively, according to the definition of drug resistance proposed by the International League Against Epilepsy. The candidate SNP loci, including ATP-binding cassette (ABC) subfamily gene ABCB1 rs2032582 and rs1045642; ABC subfamily gene ABCC2 rs717620 and rs2273697; sodium channel subunit gene SCN1A rs3812718, SCN2A rs2304016; γ-amino butyric acid type A (GABAA) receptor subunit subtype gene GABRA1 rs2279020 were genotyped following the Illumina protocols. There were no significant differences in allelic or genotypic frequencies between the drug responsive and resistant patients. The polymorphisms of the above SNP loci may not be associated with drug resistance of epilepsy in the Chinese Han population.
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… O loco rs1695 apresentou correlação com a ancestralidade europeia (-0,054) e africana (0,050), e os locos rs717620 e rs1800460 com a ancestralidade europeia. Não foi encontrada …
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Different associations between single nucleotide polymorphisms (SNPs) in cellular target, metabolism enzymes or transport proteins, and biopsy-proven acute rejection (…
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Cutaneous squamous cell carcinoma (cSCC) occurs more frequently in kidney and heart transplant recipients compared to the general population with more aggressive …
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Cutaneous squamous cell carcinoma (cSCC) occurs more frequently in kidney and heart transplant recipients compared to the general population with more aggressive …
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Mycophenolic acid (MPA) has been used as an immunosuppressive agent to prevent rejection events as a combination with calcineurin inhibitor (CNI) and corticosteroids in renal …
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Human ATP-binding cassette (ABC) transporters act as translocators of numerous substrates across extracellular and intracellular membranes, thereby contributing to …
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Long-term data on antiviral therapy in patients with HBeAg-negative chronic hepatitis B (CHB) are limited. We present the efficacy and safety of entecavir (ETV) compared with …
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Acute lymphoblastic leukemia (ALL) is the major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a …
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Cutaneous squamous cell carcinoma (cSCC) occurs more frequently in kidney and heart transplant recipients compared to the general population with more aggressive …
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… Both patients were homozygous for the C allele at position -24 in the ABCC2 gene (rs717620 of MRP2), a polymorphism which has been associated with the genetic predisposition to …
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The ATP-binding cassette transporter gene ABCB1 and the glutathione S-transferase gene GSTP1 code for a multidrug resistance protein and for a detoxifying phase II …
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Title: A Study to identify the association between polymorphisms in pharmacogenetic loci, mycophenolic acid precursors (mofetil/sodium) and clinical outcomes in renal transplant …
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To investigate the effect of single nucleotide polymorphisms in the genes for methotrexate (MTX) uptake and efflux mechanisms and in the genes of the adenosine pathway …
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To study the correlations of genetic variants of tenofovir tubular transporters, plasma tenofovir concentrations and clinical factors with decreased glomerular filtration rate in …
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The urinary coproporphyrin I /( I + III ) ratio may be a surrogate for MRP 2 activity. We conducted a prospective study in patients receiving methotrexate ( MTX ) to examine the …
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… evaluated seven SNPs in ABCC2 for impact on MPA PK and observed that promoter SNPs rs717620 (−24C>T) and rs3740066 (−3972C>T) protect renal transplant recipients from a …
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Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in …
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… rs717620 is a SNP characterized by a substitution of a G to an A in the 5′-UTR [Citation19]. Studies reporting the influence of this SNP in transporter function have associated A …
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… Moreover, 24C>T (rs717620) mutation in the gene coding for the multidrug resistance–associated protein 2 (MRP2) caused the increase in the steady-state plasma trough concentration …
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… ABCC2 - - CC genotype in rs717620 Longer PFS Akiyama et al[109] 2012 … The ABCC2 rs717620 CC genotype has been associated with a higher response rate and longer progression-…
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Genetic factors as predictor of the individual outcome of drug therapy is one aim of personalized medicine approaches. Case presentation We report a drug metabolism …
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… The influence of ABCB1 rs1128503, ABCB1 rs1045642 and ABCC2 rs717620 tested on … The effects of rs1128503, rs1045642 and rs717620 tested in a subset of patients did not …
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Over the last decade, advances in genetic technologies have accelerated our understanding of the genetic diversity across individuals and populations. Case–control and population-…
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Tenofovir disoproxil fumarate, the prodrug of nucleotide reverse transcriptase inhibitor tenofovir, shows high efficacy and relatively low toxicity in HIV patients. However, long-term …
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Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different …
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ATP-binding cassette transporter (ABC) protein group is one of the most abundant protein family exhibiting diverse functions. Proteins of this group are present and expressed in …
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Methotrexate (MTX) is used for rheumatoid arthritis (RA) treatment showing a wide toxicity profile. This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) …
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Purpose: Recent studies have proposed a link between 3 genetic markers and tacrolimus troughs and dose. The purpose of this study was to reexamine these associations of POR* 28 …
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… TDF within tubular cells, the single nucleotide polymorphism rs717620 at position −24 (C→T) of … Genetic analysis of the single nucleotide polymorphism (rs717620) of MRP2 showed …
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The risk assessment of mercury (Hg), in both humans and wildlife, is made challenging by great variability in exposure and health effects. Although disease risk arises following complex …
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… The time to first seizure analysis for SNP rs717620 (–24C>T) was statistically significant with P=0.034 but did not withstand Bonferroni correction for multiple testing (P c =0.1). …
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… In our study, the polymorphic A allele of the ABCC2 rs717620 promoter polymorphism was … found a significant association of ABCC2 rs717620 with poor histological response 31 . …
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Objectives To analyse the determinants of raltegravir CSF penetration, including the pharmacogenetics of drug transporters located at the blood–brain barrier or blood–CSF barrier. …
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Acute lymphoblastic leukemia patients after being treated with methotrexate, have differences in methotrexate serum levels and toxic side effects. One of the main determinants of these …
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… Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p= 0.004; OR= 10.7; 95% CI= 2.2-52.9) and ABCC2 CAG haplotype (p= 0.006; …
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… Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004; OR = 10.67; 95% CI = 2.15−52.85) and ABCC2 CAG haplotype (p = …
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Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1), ATP-binding cassette C2 (ABCC2) and solute carrier …
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… rs2273697 in LD with rs717620 physiologically increases the risk of drug resistance, especially to CBZ Citation[7,26]. Our cohort data from Malaysia, Hong Kong and Japan on the role …
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… We did not find any association between bilirubin levels and ABCC2 (rs717620) or NUP-153 (rs2328136). ABCC2 mediates transport of a wide range of anionic substrates into the bile, …
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… Both patients were homozygous for the C allele at position-24 in the ABCC2 gene (rs717620 of MRP2), a polymorphism which has been associated with the genetic predisposition to …
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… He was homozygous for the C allele at position-24 in the ABCC2 gene (rs717620 of MRP2), … He was homozygous for the C allele at position-24 in the ABCC2 gene (rs717620 of MRP2), …
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… The ABCC2 −24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the ABCC2 −24C>T …
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Methotrexate (MTX) is a key agent for the treatment of childhood acute lymphoblastic leukemia (ALL). Increased MTX plasma concentrations are associated with a higher risk of adverse drug effects. ATP-binding cassette subfamily C member 2 (ABCC2) is important for excretion of MTX and its toxic metabolite. The ABCC2 −24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the ABCC2 −24C>T polymorphism and methotrexate (MTX) toxicities in childhood ALL patients treated with high-dose MTX. A total of 112 Han Chinese ALL patients were treated with high-dose MTX according to the ALL-Berlin-Frankfurt-Muenster 2000 protocol. Our results showed that presence of the −24T allele in ABCC2 gene led to significantly higher MTX plasma concentrations at 48 hours after the start of infusion, which would strengthen over repeated MTX infusion. The −24T allele in ABCC2 gene was significantly associated with higher risks of high-grade hematologic (leucopenia, anemia, and thrombocytopenia) and non-hematologic (gastrointestinal and mucosal damage/oral mucositis) MTX toxicities. This study provides the first evidence that the −24T allele in ABCC2 gene is associated with the severity of MTX toxicities, which add fresh insights into clinical application of high-dose MTX and individualization of MTX treatment.
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The aim of this study is to analyze polymorphisms in genes involved in 6-mercaptopurine detoxification (TPMT); methotrexate (MTX) metabolism including ABCB1 (or MDR1), ABCC2, SLC19A1 (or RFC1), and SLCO1B1; and the MTX effect mainly MTHFR and TYMS, and to assess whether these polymorphisms are predictors of treatment toxicity and/or MTX clearance. Materials and methods This study included 127 Lebanese acute lymphoblastic leukemia patients, of whom 117 were treated following the St Jude’s Children Research Hospital protocol. Genotyping was performed using real-time PCR or restriction fragment length polymorphism. MTX levels were measured using a polarization fluorescence assay from Roche. MTX clearance was estimated on the basis of all available MTX levels measured after high-dose MTX treatment during the consolidation phase. Results Five variants in four genes (MTHFR, ABCB1, ABCC2, and TYMS) were shown to be associated with toxicity, but neither was associated with MTX pharmacokinetic parameters. For instance, during the consolidation phase, a statistically significant association was found between MTHFR rs1801133 variant allele carriers and a decrease in hemoglobin levels [odds ratio (OR)=3.057; 95% confidence interval (CI): 1.217; 7.680]. In addition, a statistically significant association was found among neutropenia (absolute neutrophil count<500) and variant allele carriers of ABCB1 rs1045642 (OR=5.174; 95% CI: 1.674; 15.989) and ABCB1 rs1128503 (OR=3.364; 95% CI: 1.257; 9.004), respectively. ABCC2 rs717620 variant allele carriers needed significantly more time to reach a MTX level below 0.1 µmol/l (&bgr;=5.122; 95% CI: 1.412; 8.831). During the continuation phase, a statistically significant association was found between ABCC2 rs717620 and TYMS 28-bp tandem repeats carriers with the need to decrease weekly MTX doses (&bgr;=−4.905; 95% CI: −9; −0.809 and &bgr;=−5.770; 95% CI: −10.138; −1.403), respectively. Conclusion Genotyping for MTHFR, ABCB1, ABCC2, and TYMS polymorphisms may be useful in identifying patients at risk of increased MTX toxicity and the need for dose optimization before treatment initiation.
464
Earlier studies have indicated that the pharmacokinetics of mycophenolic acid (MPA) is influenced by polymorphisms of ABCC2, which encodes for the membrane transporter MRP2. The ABCC2 rs717620 A allele has been associated with enterohepatic recirculation of MPA, and our previous work had correlated the discontinuance of MPA with this allele in pediatric heart transplant patients. Therefore, we hypothesized that the ABCC2 rs717620 A allele would be associated with poorer outcomes including rejection with hemodynamic compromise (RHC), graft failure, and death in the pediatric heart transplant (PHTx) population receiving MPA.
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… Although human ABCC2 displays the functional -24C>T polymorphism (rs717620), most of the studies failed to find an association with MPA treatment course Citation[40,45,46]. …
466
A number of studies have demonstrated that ABCB1 and BCRP (ABCG2) actively transport Aβ. We aimed to investigate the association of genetic variants of selected multidrug …
467
… In a study of patients with small cell lung cancer, SNP rs717620 in ABCC2 was moderately associated with poor response to chemotherapy but strongly associated with progression-…
468
The aim of this study was to evaluate the association of genetic variants in the major genes involved in carbamazepine (CBZ) metabolism and transport with its pharmacokinetics in …
469
We describe here the case of a 60-year old male patient treated for an extensive local progression of a pleiomorphic sarcoma on the right tibial crest with second-line trabectedin. Two …
470
… For the genotype analysis, the relationship between the SNP rs717620 in the ABCC2 gene (… The previous association was observed when the rs717620 polymorphism was part of the …
471
To evaluate pharmacogenetic factors as contributors to the variability of unbound mycophenolic acid ( MPA ) exposure in adult allogeneic haematopoietic cell transplantation ( …
472
This paper reviews the impact of genetic variability of drug metabolizing enzymes, transporters, receptors, and pathways involved in chronic pain perception on the efficacy and safety of …
473
… Genetic variants (like rs717620) of ABCC2 can affect the population pharmacokinetic modeling MTX. ABCC2-24T allele (rs717620) had a combined influence on both MTX elimination …
474
High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate …
475
Tacrolimus is an immunosuppressive drug used for the prevention of the allograft rejection in kidney transplant recipients. It exhibits a narrow therapeutic …
476
Several statins are substrates for the multidrug resistance-associated protein 2 transporter, encoded by the ABCC2 gene. We analyzed in the Rotterdam Study whether the common …
477
Pitavastatin, a 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitor is distributed to the liver, a target organ of action and excreted mainly into the bile. To investigate the impact of …
478
Pharmacogenetics correlates certain genetic variants, such as single nucleotide polymorphisms (SNPs), with blood drug levels, efficacy, and adverse effects of the treatment. Tacrolimus …
479
Pharmacogenetic study of cytochrome P450 (CYP) gene CYP2D6 and tamoxifen outcomes remain controversial. Apart from CYP2D6, other drug-metabolizing enzymes …
480
… , focused on ABCC2, reporting a significant association of rs717620 with response and a progression-free survival. These hypotheses-generating studies were carried out on two …
481
… The polymorphism rs717620 enhances transport activity and substrate excretion [35, 36]. Subjects with a mutated allele (T) of rs717620 tended to progress from IGT to diabetes mellitus (…
482
… Four polymorphisms (rs1885301, rs7910642, rs2804402 and rs717620) were considered cosmopolitan and were found at >5% frequency in each ethnic population. The −798C>A, −…
483
… The ABCC2 promoter variant rs717620 has been previously shown to be associated with … ABCC2 haplotypes containing rs717620 were also shown to be associated with hepatocellular …
484
… Pyrosequencing analysis revealed that the patient was wild type for the ABCC4 but heterozygous for the ABCC2 rs717620 C>T and ABCC10 rs2125739 T>C polymorphisms. …
485
Purpose Increasing evidence suggests that genetic variants from ABCC 2 transporter may be associated with an altered response to antiepileptic drugs ( AED s). However, the …
486
… Our own results suggest an association of the nonsynonymous SNP rs717620 in ABCC2 … Genotyping for rs4149056, rs11045879, and rs2306283 in SLCO1B1; rs717620 in ABCC2; …
487
… In particular, ABCC2 rs717620 has been previously associated with decreased protein … In addition, ABCC2 rs717620 and ABCC2 rs3740066 have a combined effect in increasing …
488
… We prospectively investigated the influence of four common ABCC2 genetic variants (rs717620… The population pharmacokinetics modelling showed that ABCC2 −24T allele (rs717620) …
489
… ABCC2 rs717620 variant allele carriers needed significantly more prolonged time to reach … significant association was shown between ABCC2 rs717620 and TYMS 28 bp tandem …
490
The discovery of pharmacogenomic markers in colorectal cancer (CRC) could be setting-specific. FOLFOX4 is employed in the adjuvant and metastatic setting in CRC. This prospective study is aimed to validate in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting (that is, GSTP1-rs947894, and-rs1138272; GSTM1-null genotype; AGXT-rs4426527,-rs34116584 and del-74 bp), and to discover additional markers. CRC patients (n= 144) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes. Grade⩾ 2 neurotoxicity was associated (false discovery rate-adjusted q-value< 0.1) with single-nucleotide polymorphisms in ABCC1 (rs2074087: odds ratio= 0.43 (0.22–0.86)), and ABCC2 (rs3740066: 2.99 (1.16–7.70); rs1885301: 3.06 (1.35–6.92); rs4148396: 4.69 (1.60–13.74); rs717620: 14.39 (1.63–127.02)). hMSH6-rs3136228 was associated with grade 3–4 neutropenia (3.23 (1.38–7.57), q-value= 0.0937). XRCC3-rs1799794 was associated with grade 3–4 non-hematological toxicity (8.90 (2.48–31.97), q-value= 0.0150). The markers previously identified in metastatic CRC were not validated. We have identified new markers of toxicity in genes of transport and DNA repair. If validated in other studies, they could help to identify patients at risk of toxicity.
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目的: 研究肾移植术后患者多药耐药相关蛋白 (MRP2/ABCC2) 基因多态性对环孢素 (CsA) 肝功能异常的影响. 方法: 入选的 339 例肾移植受者均采用 CsA 治疗, 检测患者 rs717620 (A/G) 和 rs2273697 (G/A) 多态性的基因型. 此外, 采用荧光偏振免疫法检测患者的 CsA 血药浓度, 根据肾移植患者发生肝脏损伤的情况分为 3 组. 结果: rs717620 和 rs2273697 突变等位基因发生频率分别为 38.89% 和 10.72%. ABCC2 基因 rs717620 位点的 G 突变等位基因与 CsA 肝功能异常的发生密切相关, 与对照组比较, CsA 肝功异常组的 GG 基因型发生频率明显升高 (P< 0.05), AA 基因型发生频率明显降低 (P< 0.05). ABCC2 基因 rs2273697 多态性与 CsA 肝功异常的发生无明显相关. 基因型分析结果显示, 这两个多态性对 CsA 谷浓度均无明显相关性, 但 rs2273697 多态性对 ALT 和 AST 检测值有明显影响. 对于 ABCC2 基因 rs717620 而言, GG 基因型纯合子携带者的发病风险比 AA 型纯合子携带者高 6 倍 (OR= 6.960, 95% CI: 1.636~ 29.610, P< 0.01). 单倍体分析结果显示, 与 AA-AA 基因型个体相比, GG-GG 和 GG-GA 基因型个体移植术后发生 CsA 肝功异常的风险分别增加 5.909 倍和 13.333 倍. 结论: ABCC2 基因 rs717620 位点多态性与 CsA 肝功异常有明显相关性. ABCC2 基因单倍体各基因型中, GG-GG 和 GG-GA 单倍体基因型是肾移植术后发生 CsA 肝功异常的危险基因因素.
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To investigate the association between cyclosporine (CsA) induced liver disfunction and multidrug resistance-association protein 2 (MRP2/ABCC2) genetic polymorphisms in Chinese renal transplant recipients. METHODS: 339 renal allograft recipients were included in this study which were all treated by CsA. Two SNPs (rs717620 A/G; rs2273697 G/A) in chr. 10 were genotyped. Besides, the CsA whole blood levels of renal transplant recipients were measured by fluorescence polarization immunoassay. All the subjects were divided into three groups according to the liver injury occurrence. RESULTS: The frequencies of rs717620 and rs2273697 mutation allele were 38.89% and 10.72%, respectively. The ABCC2 gene rs717620 SNP, G mutation allele was strongly associated with CsA induced liver disfunction. Compared with the control group, the distribution frequency of the GG genotype was significantly increased in CsA induced liver disfunction group (P< 0.05), and that of the AA genotype was significantly increased (P< 0.05). The ABCC2 gene rs2273697 polymorphism was not strongly associated with CsA hepatotoxicity. Genotype analysis revealed that there was no significant associations between these two SNPs and cyclosporine trough concentrations. But a positive association between rs2273697 polymorphism and ALT, AST concentrations was obse rved. The risk of disease for homozygous GG carriers was 6-fold higher (OR= 6.960, 95% CI: 1.636-29.610, P< 0.01) in comparison with AA carriers in rs717620 gene. Analysis of haploid showed that compared with individuals carrying AA-AA, the risks of CsA induced liver disfunction after transplantation in the individuals carrying GG-GG and GG-GA were 5.909 and 13.333-fold higher, respectively. CONCLUSION: There is an association between the rs717620 genetic polymorphism in exon 1 of ABCC2 gene and CsA induced liver disfunction. The haploids carrying GG-GG and GG-GA have higher risk to result in CsA induced liver disfunction.
493
Factors that would predict treatment outcome for methotrexate (MTX) would be of great value to clinicians. Recent pharmacogenetic studies have reported associations between single nucleotide polymorphisms (SNP) in MTX transporters and treatment outcome in childhood acute lymphoblastic leukemia and in rheumatoid arthritis.
494
Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and …
495
The efficacy of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) patients has significantly increased in the last 20 years; as a result, the focus of research is slowly shifting …
496
Results: The BCRP G34A SNP was the only SNP significantly associated with ALL. Risk factors included pre-treatment WBC counts and post-treatment peripheral and bone marrow …
497
Carbamazepine (CBZ) is one of the most widely used antiepileptic drugs. The aim of the present study is to investigate the impacts of polymorphisms in genes related to …
498
This exploratory retrospective study examined the effects of polymorphisms in transporter genes related to irinotecan pharmacokinetics and those in genes related to irinotecan …
499
Inter-individual variability of pharmacokinetics may account for unpredictable toxicities of docetaxel. Methods From March 2007 to June 2008, female patients with operable …
500
Unusual drug accumulation is a common mechanism underlying serious drug-induced liver injury. Polymorphisms in three drug transporter genes (ABCB1, SLCO1B1 and ABCC2) may …
501
Delayed graft function (DGF) is an important complication in renal transplantation, contributing significantly to decrease in long‐term allograft survival. In addition to donor‐ and recipient…
502
This study was designed to determine whether genetic polymorphisms of multidrug-resistant protein 2 (ABCC2), organic anion transporting polypeptide 1B1 (SLCO1B1), and breast …
503
Background. Tenofovir is a widely used antiretroviral drug although it can cause kidney tubular dysfunction (KTD). The aim of this study was to determine the association between …
504
Objective. Although methotrexate (MTX) is the most widely prescribed drug in juvenile idiopathic arthritis (JIA), 30% of patients fail to respond to it. To individualize treatment strategies, …
505
Objectives Methotrexate (MTX) is a cheap and efficacious drug in juvenile idiopathic arthritis (JIA) treatment. If JIA patients are unresponsive to MTX, early and effective combination …
506
BACKGROUND: Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal …
507
Methotrexate (MTX) is often used to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, MTX has …
508
Background Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal …
509
This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in …
510
… Two of the MRP2 SNPs that we evaluated (rs1885301 and rs717620) are situated 1,500 base pairs apart, both at the 5 end of the gene, which is associated with regulation of gene …
511
ATP‐binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the …
512
Aim: The present study aimed to investigate the associations between variants in pharmacokinetic- and pharmacodynamic-related genes with the dosages, concentrations and …
513
Multidrug-associated protein 2 (MRP2) is an efflux transporter that is expressed at the bile canalicular membrane. To allow in vitro to in vivo extrapolation of the contribution of MRP2 toward hepatic disposition of its substrates, data on the interindividual variability of hepatic MRP2 protein expression are required. Therefore, we quantified the expression of MRP2 in the University of Washington (UW) human liver bank (n = 51) using a modified version of a previously validated liquid chromatography/tandem mass spectrometry assay. An unlabeled (LTIIPQDPILFSGSLR) and stable isotope-labeled (LTIIPQDPILFSGSL[13C615N1]R) surrogate peptide for MRP2 were used as the calibrator and internal standard, respectively. After isolation of the membrane fraction from the liver tissue, in-solution tryptic digestion was conducted. Quality control samples created by spiking human serum albumin or pooled human liver (n = 51) matrix with three different MRP2 synthetic peptide concentrations generated error and precision values of less than 15%. As determined by the surrogate peptide, the average MRP2 expression in the UW liver bank samples was 1.54 ± 0.64 fmol/μg liver membrane protein and was found to be independent of age (7–63 years) or sex. A single nucleotide polymorphism in the promoter region (rs717620), previously thought to affect MRP2 expression, did not influence hepatic expression of MRP2. In contrast, the single nucleotide polymorphism 21214G>A (V417I; rs2273697) was associated with significantly higher hepatic MRP2 expression.
514
To study the influence of gene mutation to statin responsiveness on high-risk cardiovascular disease (CVD) population in Chinese. Methods This study collected 318 subjects of Chinese Han aged 20–70 years, who need statins treatment according to ‘Chinese guidelines on prevention and treatment of dyslipidemia in adults’ in 2007. Atorvastatin was taken 20 mg every night from first day of taken drugs to the end of 4 weeks. Statin responsiveness related to gene mutation was analysed. Results (1) The relationship between genotypes of 144 SNP with LDL-C change% was analysed, 5 SNP were found to have significantly difference, which is rs2235013, rs2235033, rs1128503, rs10276036 of ABCB1 gene and rs717620 of ABCC2 gene. (2) The correlation between SNP and statin responsiveness were analysed in three genetic models, the results showed that the significant difference can be seen in the additive and dominant models of rs717620 and additive model of rs2235033 after adjusted for age, sex, BMI and baseline LDL-C levels. (3) Multivariable analysis on the correlation between rs1128503 and rs717620 with LDL-C change% indicated that striking differences were observed for LDL-C change% across two genotypes of two SNPs. Compared with the wild genotypes, carriers of mutant genotypes had 78% increased risk or 59% decreased risk. Statin response was compared under the joint effects of two SNPs under study involving the same pathway. Our results indicated that the joint effects of these two SNPs were significantly higher than that of respective one, LDL-C change% increased one times in group of rs1128503 wild+rs717620 mutant compared with group carried two wild genotypes. Conclusions Genes encoding ABCB1 and ABCC2 may be logical candidates for statin response among Chinese with high CVD risk. The joint effect of two SNPs within these two genes was more obvious than any single SNP.
515
Some study found that ATP‐binding cassette (ABC) efflux transporters play an important role in antiepileptic drug resistance, especially ABCB1 and ABCC2. The aims of this study were to evaluate the relationship between the genetic polymorphisms of ABCC2 and ABCB1 and the therapeutic efficacy of antiepileptic drugs (AEDs) in Chinese epileptic patients. Methods:ABCB1 rs1045642 (3435C>T) and ABCC2 rs717620 (−24C>T), rs3740066 (3972C>T), and rs2273697 (1249G>A) polymorphisms loci in 537 Chinese epilepsy patients (217 drug resistant patients and 320 drug responders) were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Results:ABCC2 rs717620 −24TT genotype was significantly associated with drug resistant epilepsy (odds ratio [OR]= 4.06 [1.79–9.20], P= 0.001). The OR values of ABCC2 rs717620 −24 CT+TT genotypes and ABCC2 rs3740066 (3972C>T) CT+TT genotypes were markedly higher in drug resistant patients (OR = 1.57 [1.08–2.29], P= 0.018; OR = 1.49 [1.02–2.18], P= 0.038, respectively) compared with responsive patients. ABCC2 rs2273697 (1249G>A) and ABCB1 rs1045642 (3435C>T) polymorphisms were not associated with drug resistant epilepsy. Linkage disequilibrium (LD) test showed that the ABCC2 rs717620 were in strong LD with rs2273697 (D’= 0.694) and rs3740066 (D’= 0.699). The frequencies of haplotypes TGT (ABCC2 −24C>T/ABCC2 1249G>A/ABCC2 3972C>T) in resistant patients was significantly higher than those in responsive patients (21.0% vs. 14.2%, P < 0.05). Conclusion:ABCC2−24C>T, 3972C>T polymorphisms and one ABCC2 haplotype is associated with AED resistance; ABCC2 1249G>A and ABCB1 3435C>T polymorphisms are not associated with AED resistance in our study. These data suggest that ABCC2 polymorphisms and haplotype may affect the response of antiepileptic drugs.
516
Both Fluoropirimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat lung, colorectal, ovarian, breast, head/neck, and genitourinary cancers. However, the efficacy of FluOx-based therapy is often compromised because of the severe risk of toxicity. Stratification of patients for multidrug response is a promising strategy for cancer treatment and personalized therapy.
517
Medical Department, SHS Aabenraa, Aabenraa, Denmark, Institute of Regional Health Service Research, University of Southern Denmark, Odense, Denmark, Medical Department, Viborg Regional Hospital, Viborg, Denmark, Danish Cancer Society Research Center, Copenhagen, Denmark, National Research Centre for the Working Environment, Copenhagen, Denmark, and National Food Institute, Technical University of Denmark, Soborg, Denmark
518
… 24C>T or rs717620), has been associated with higher response rates and longer progression-free survival in advanced NSCLC patients from Korea receiving irinotecan and cisplatin. …
519
Nogo-B, also known as reticulon 4B, belongs to the reticulon family of proteins that primarily resides in the endoplasmic reticulum (ER) and regulates ER structure. In the …
520
… The ABCC2 -24C>T (rs717620) SNP has an allele frequency of ~18%, and is associated with decreased MRP2 function (Pharmacogenomics J 11:25, 2011). We investigated the effects …
521
… An additional SNP in ABCC2 (–24C>T, rs717620) has been associated with lack of response to CBZ in young Caucasian epilepsy patients 6 . …
522
MicroRNAs (miRNAs) are important regulators of gene expression that control physiological and pathological processes. A global reduction of miRNA abundance and function is a …
523
We performed the Drug Metabolizing Enzymes and Transporters (DMET) platform analyses in a cohort of colorectal cancer (CCR) patients receiving fluorouracil, folinic acid and …
524
To determine the association between polymorphisms of the multidrug transporter genes ABCC2, ABCC5 and ABCG2, and drug resistance in epilepsy by genotyping …
525
… nucleotide polymorphisms (SNPs) in this gene are located 1549 (G>A; rs rs1885301), 1410 (A>G; rs1885301), 1023 (G>A; rs7910642), 1019 (A>G; rs2804402) and 24 (C>T; rs717620) …
526
ABCC2 (MRP2) is an important export pump, expressed at tissue barriers. The genetic variants− 24C> T, 1249G> A and 3972C> T are leading to inter-individual differences of …
527
… Two SNPs in ABCC2 (rs3740066 and –24 C>T rs717620) are also associated with neuropathy risk. rs717620 has been associated with decreased ABCC2 function in vitro 23–25 and …
528
Platinum-based chemotherapy is the most common treatment for non-small cell lung cancer (NSCLC), and expression levels of drug metabolism and transport proteins are correlated …
529
MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin‐Johnson syndrome due to mutation in ABCC2 gene …
530
Abstract 3650 Background: Mantle cell lymphoma (MCL) is an aggressive lymphoma with poor prognosis. Cyclin D1 (CCND1) gene amplification is a marker of MCL. Glutathione (GSH) …
531
… Next, in a cohort of 108 human subjects, we observed that homozygosity for a common reduced-function variant in ABCC2 (rs717620) was also linked with increased erythromycin …
532
… Next, in a cohort of 108 human subjects, we observed that homozygosity for a common reduced‐function variant in ABCC2 (rs717620) was also linked to an increase in erythromycin …
533
… We have elsewhere shown an association between the ABCC2 SNP, rs717620 and its haplotype, CGTC (consisting of the associated rs717620C allele) with KTD [16]. Haploview was …
534
… We did not observe differences in discontinuation rates associated with ABCC2 rs717620 genotypes (Figure 1C). The final Cox analysis identified body weight as significant covariable. …
535
… (ABCC2) gene rs717620 were individually and significantly … The strength of associations between rs717620 CNT, … Under the dominant genetic mode, carriers of rs717620 T allele …
536
… (ABCC2) gene rs717620 were individually and significantly … The strength of associations between rs717620 CNT, … Under the dominant genetic mode, carriers of rs717620 T allele …
537
… For the FOLFIRI/placebo arm only, the ABCC2 gene SNP rs717620 was associated with … Conclusions: Presence of the T allele in the ABCC2 gene at rs717620 was associated with …
538
… between ABCC2 gene rs717620 and ABCB1 rs1128053 … Under the dominant genetic mode, carriers of rs717620 T allele … Haplotype rs717620 T and rs1128503 T alleles had …
539
We investigated the influence of rAAV1 mediated beta1-adrenergic receptor gene overexpression on metoprolol antihypertensive effect of spontaneously hypertensive rats.
540
WHO defined health in a way as 'physical, mental and social well-being'. Now it is well known that physical illness can induce a mental disorder. Is there any relevance between physical and mental sub-health status? Do they influence each other, and which one is more important? Our hypothesis was that mental sub-health might interact with physical sub-health. Our objectives were (1) to find psychological characteristic in physical sub-health persons, and (2) to identify the relationship between mental and physical sub …
541
The introduction of highly active anti-retroviral therapy has led to a significant decline in morbidity and mortality. Although several studies in adult populations have shown that tenofovir-disoproxilfumarate (TDF) use is associated with a significant loss of renal function, there is still uncertainty on the long-term TDF safety profile in pediatric HIV populations, mostly in vertically HIV-infected patients. The aim of this study was to evaluate the long-term TDF renal safety profile, during a ten-year follow up. Methods Twenty-six vertically HIV-infected patients were evaluated for a total of 132 months of follow up, monitoring anthropometric parameters, renal function, viral load and CD4? count. Generalized estimating equations were used to evaluate the changes in anthropometric and laboratory variables. Multivariable fractional polynomials were used to test for the existence of non-linear relationships of outcomes with time and other continuous covariates. In all patients, weight, height and body mass index increased linearly with time. CD4? count and glomerular filtration rate decreased linearly with time (p\0.01). Results No significant increase of serum creatinine was registered. An inverse linear relationship between time and plasma phosphate was found. Hypophosphatemia was detected in 17 patients, mostly mild. In 14 out of 17 we also genotyped single nucleotide polymorphisms rs717620 mapping in ABCC2, a gene encoding for a renal transporter. Conclusions Our study demonstrates the relative safety of prolonged use of TDF in vertically HIV-infected children and young adults. The most relevant alteration that emerged was hypophosphatemia, appearing after 72 months of TDF therapy, mostly mild and without clinical significance.
542
A variabilidade de resposta aos medicamentos ocorre tanto dentro de populações como entre populações. A análise de polimorfismos genéticos que possam explicar tal variação é …
543
This study aimed to determine the influence of gene candidates on mycophenolic acid (MPA) response during the first year of renal transplantation. Materials & methods: A total of …
544
Polymorphic genes of drug metabolizing enzymes and transporters may influence drug response. With some exemptions, single nucleotide polymorphisms in such genes, however, are …
545
… These SNPs presented low P values and were located in genes of potential interest; rs717620 in ABCC2 (P=2.20×10 −4 ), earlier associated with decreased promoter activity and …
546
… The ABCC2 rs717620 A variant was significantly associated with GI intolerance leading to drug discontinuation (p < 0.001); the IMPDH1 rs2278294 A variant and rs2228075 A variant …
547
Mycophenolate mofetil (MMF) is an effective and commonly used immunosuppressant but has frequent adverse events. Genetic polymorphisms may contribute to variability in MMF efficacy and related complications. In this study we explore the distribution frequencies of common single nucleotide polymorphisms (SNPs) of IMPDH1, IMPDH2 and ABCC2 and investigate whether these SNPs influence MMF adverse events in 59 pediatric heart recipients. Methods Genotypes were assessed by TaqMan analysis of: ABCC2 rs717620; IMPDH2 rs11706052; and IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294 and rs2228075. Gastrointestinal (GI) intolerance was defined as diarrhea, vomiting, nausea or abdominal pain requiring dose-holding for >48 hours or MMF discontinuation. Bone marrow toxicity was evaluated using Common Terminology Criteria for Adverse Events Version 3 (CTCAE). Results GI intolerance occurred in 21 patients, and 21 had bone marrow toxicity. The ABCC2 rs717620 A variant was significantly associated with GI intolerance leading to drug discontinuation ( p IMPDH1 rs2278294 A variant and rs2228075 A variant were also associated with greater GI intolerance ( p = 0.029 and p = 0.002, respectively). The IMPDH2 rs11706052 G variant was associated with more frequent neutropenia requiring dose-holding ( p = 0.046). Conclusions In this small sample of pediatric heart transplant patients receiving MMF, ABCC2 , IMPDH1 and IMPDH2 SNPs were associated with MMF GI intolerance and bone marrow toxicity. Thus, genetic polymorphisms may directly influence MMF adverse events.
548
The ATP-Binding-Cassette (ABC) superfamily of transporters, implicated in the traffic of drugs/xenobiotics across membranes, represents one of the larger families of drug-response …
549
Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is limited by partially dose-dependent side-effects. Predictors of therapeutic response may result in …
550
The aim of this study was to develop a population pharmacokinetic model of tacrolimus in pediatric kidney transplant patients, identify factors that explain variability, and determine …
551
… The genotypes for the MRP2 C-24 T (rs717620) and UGT2B7 C802 T (rs7439366) SNPs were determined using real-time quantitative polymerase chain reaction assay based on the 5' …
552
NSCLC is the leading cause of cancer-related death in the US. Patients with NSCLC are mostly treated with platinum-based chemotherapy, often in combination with radiation therapy. …
553
Polymorphisms of MRP2 (ABCC2) are associated with susceptibility to nonalcoholic fatty liver disease
We hypothesized that ABCC2 gene variants may contribute to susceptibility to nonalcoholic fatty liver disease (NAFLD). Additionally, we tested the hypothesis of a relation between gene variants and disease severity. Patients and Methods The study involved 167 individuals: 109 consecutively presenting unrelated patients with features of NAFLD and different stages of disease severity, and a group of 58 healthy individuals. Four tag single-nucleotide polymorphisms (SNPs; rs717620 A/G, rs2756105 C/T, rs2002042 C/T and rs3740066 A/G) representing 46 polymorphic sites (r2>.8) were genotyped. Furthermore, two additional SNPs (rs17222723 A/T and rs8187710 G/A) were included. Results On univariate analysis, after multiple comparison correction by permutation tests, there were significant differences observed in the allele frequencies of rs17222723 and rs8187710 between healthy individuals and NAFLD patients (empirical P=.037 and .035, respectively). Allelic odds ratios [95% confidence interval] for rs17222723 and rs8187710 were 2.80 [1.11–7.04] and 2.80 [1.11–7.04], respectively. When we tested the hypothesis of a relation between gene variants and the clinical and histological spectra of NAFLD by multinomial regression analysis, a significant association was observed with the same markers: rs17222723 (P=.0029) and rs8187710 (P=.015). Conclusions Our study suggests a potential role of ABCC2 in susceptibility to NAFLD and disease severity.
554
Idiosyncratic hepatotoxicity accounts for one in five cases of acute liver failure with 60–80% mortality without liver transplantation (Kaplowitz, 2005). The DILIGEN study is a UK-wide …
555
We hypothesized that common genetic variation at ABCC2 influences ICP susceptibility. Hence we studied the association of single nucleotide polymorphisms (SNPs) of promoter, coding and non-coding regions of ABCC2 and intrahepatic cholestasis of pregnancy (ICP). Methods 70 ICP patients and 112 healthy pregnant women in the third trimester of their pregnancies were included in a cross sectional study. Four tag SNPs (rs717620 A/G; rs2756105 C/T; rs2002042 C/T; rs3740066 A/G) encompassing 70 kb in chr.10 and representing 46 polymorphic sites ( r 2 >0.8) were genotyped. Besides, 2 additional SNPs (rs17222723 A/T and rs8187710 G/A) were included. Results In univariate analysis, rs2002042 and rs3740066 were significantly associated with ICP ( p p ABCC2 gene in ICP patients significantly differed from controls ( p Conclusions We found an association between the rs3740066 in exon 28 of ABCC2 gene and ICP. The risk of disease for homozygous AA carriers is 4-fold higher (OR 4.44 CI 95% 1.83–10.78...
556
Peripheral neuropathy is a major adverse effect seen in multiple myeloma (MM) patients treated with thalidomide, with rates varying between trials from 15% to 70%. Peripheral neuropathy can often lead to ongoing impairment of quality of life and can lead to discontinuation of treatment. Identifying patients at risk of neuropathy and understanding its pathogenesis would be a significant step forward in the management of thalidomide based therapy. Proposed mechanisms have included: Anti-angiogeneic properties of thalidomide leading to a reduction in nerve blood supply; direct toxic effects of thalidomide on neurons of the posterior root ganglia and dysregulation of neurotrophin activity through effects of thalidomide on NFkB. Genetic variation in genes important in the mechanism of thalidomide neurotoxicity are likely to impact on whether an individual patient develops this adverse effect. Taking a nested case control approach we used peripheral blood DNA from 388 Caucasian MM patients all who had received induction thalidomide (200mg) as part of the Myeloma IX trial. Samples from 80 patients that developed sensory-motor peripheral neuropathy in response to thalidomide therapy were available for this analysis, these were age and sex matched with a ratio of one case to 4 controls. We assayed 3403 SNPs in coding and predicted regulatory regions selected in 1266 genes previously shown to be involved in the pathogenesis, treatment response and side effects associated with myeloma and its therapy. SNPs were present on a custom-built Affymetrix® targeted genotyping chip (designed by “Bank on a Cure” (BOAC)), which utilizes molecular inversion probe technologies. We carried out a univariate analysis by Fischer exact tests. Due to the large number of SNPs and relatively small number of samples, we chose to correct for multiple testing using label swapping permutation using the program PLINK. The most significant SNPs associated with thalidomide related peripheral neuropathy are listed with p=permutated empirical p-value and OR=Odds Ratio: ABCC2-Ile1324Ile (p
557
The cause of Rotor syndrome (RS), a rare‐familial conjugated hyperbilirubinaemia with normal liver histology, is unclear. We hypothesized that RS can be an allelic variant …
558
Diclofenac is a widely used nonsteroidal anti-inflammatory drug and is among the most common drugs causing idiosyncratic hepatotoxicity in several recent series …
559
Type I HRS is characterized by rapidly progressive functional renal failure in subjects with cirrhosis and is associated with a 90 day mortality exceeding 90%. Uncontrolled …
560
It is unclear whether hepatitis C virus (HCV) is eradicated in patients with chronic hepatitis C who achieve a sustained virologic response [SVR). During this long-term …
561
It is unclear whether hepatitis C virus (HCV) is eradicated in patients with chronic hepatitis C who achieve a sustained virologic response [SVR). During this long-term …
562
It is unclear whether hepatitis C virus (HCV) is eradicated in patients with chronic hepatitis C who achieve a sustained virologic response [SVR). During this long-term …
563
… All group 2 subjects were genotyped for the −24 C→T SNP (rs717620) in exon 1 and for the 1249 G→T SNP (Val417Ile; rs2273697) in exon 10 of the ABCC2 gene by 5′ nuclease …
564
Objective The adenosine triphosphate‐binding cassette (ABC) class transporter ABCC2 (MRP2 [multidrug resistance related protein 2] or cMOAT [canalicular multispecific organic …
565
Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia and caused by mutations of the ATP-binding cassette (ABC) …
566
We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in eight genes encoding the ATP-binding cassette, subfamily C (ABCC/MRP/CFTR), by …
567
We found nucleotide variability in the 5′-upstream region and exonic sequences of a gene-encoding canalicular multispecific organic anion transporter/multidrug resistance-…
568
Epilepsy is a common, chronic and treatable neurological disorder. Mesial temporal lobe epilepsy (MTLE) is the more frequent and refractory among parcial epilepsies. About fourth per …
569
Twenty years ago, Gerard SIEST visited for the first time Santorini. I can’t say that I remember much or that it enchanted him. I remember a terrifying in my eyes, uphill dirt road from the …
570
To expand the number of characterized PGx variants and genes, 137 Coriell cell lines were selected based on partial genotype characterization from several sources. DNA …
571
The objective of this study was to investigate the influence of multidrug resistance protein (MRP), MRP-2-24C> T polymorphism on the pharmacokinetics of mycophenolate mofetil in …
572
MicroRNAs (miRNAs) are important regulators of gene expression that control physiological and pathological processes. A global reduction of miRNA abundance and function is a …
573
… O alelo variante de rs717620 foi associado neutropenia em graus acima de 1 (p=0,040, OR=0,261). O alelo ancestral de rs3740066 foi associado ao aumento da creatinina sérica em …
574
… and rs717620, have been significantly associated with European Alliance of Associations for Rheumatology (EULAR) good or moderate response, while rs3740066 and rs717620 were …
575
1 Supplementary Material S1. Characteristics of 247 candidate SNPs selected to assess MeHg-gene interactions Page 1 1 Supplementary Material S1. Characteristics of 247 candidate …
576
Linezolid is an oxazolidinone active against Gram-positive bacteria and it inhibits the mRNA binding to the ribosome. It is a methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumonia, vancomycin-resistant enterococci and multi-drug resistant tubercolosis therapy option. This drug is not a cytochrome P450 system substrate and it is mainly excreted by kidney. The efficacy predictive index based on AUC/MIC (AUC, area under the antimicrobial concentration-time curve for 24hs; MIC, minimum inhibitory concentration) is above 100 [1]. Theoretical efficacy cut-off values were minimum serum concentration (Cmin)≥ 2mg/L and/or AUC> 160-200mg/h/L (9)[2]. Cmin> 10mg/L and/or AUC> 400mg/h/L were associated to drug overexposure [3]. Pharmacogenomics and therapeutic drug monitoring could contribute to enhance the antimicrobial therapy optimization on the basis of interindividual genetic variability [5]. This study suggests, despite the confounding factors associated to ICU patients, for the first time, the usefulness of genetic-based linezolid therapy and highlights the needed of therapy personalization. However, further studies, in larger and different cohorts, are required to confirm this data and to clarify the role of the evaluated SNPs in linezolid pharmacokinetics.
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