rs17222723

Review article on pharmacogenetics of platinum-based chemotherapy in ovarian cancer. Discusses ABCC2 polymorphisms including rs17222723 (V1188E), rs717620, and rs2273697. Highlights that while single variants show modest associations with platinum sensitivity and toxicity, their inclusion in a multi-gene pharmacogenetic score significantly improves prediction of progression-free survival and toxicity risk. Emphasizes the clinical utility of combinatorial models over single SNP analysis.

2027 · Gagno Sara, Arrigo Giulia, Cecchin Elena, Toffoli Giuseppe, Hattinger Claudia Maria

Forensic genetic study investigating the influence of polymorphisms in drug metabolism and transporter genes on Tramadol (TR) pharmacokinetics in post-mortem cases. The study analyzed 73 loci in UGT1A8, ABCC2, SLC22A1, and CYP2D6 genes in fatalities involving Tramadol. Significant correlations were found between several ABCC2 loci (including rs17222723/V1188E and others within the gene) and Tramadol metabolic ratios (M2/M1, TR/M2, TR/M1). The findings suggest that ABCC2 polymorphisms may alter Tramadol efflux and clearance, potentially leading to unsatisfactory therapeutic effects or increased risk of toxicity and fatal outcomes. The study highlights the utility of pharmacogenomic profiling in forensic toxicology to explain inter-individual variability in drug response and lethality.

2025 · Authors vary by specific forensic cohort (e.g., Spanish or European forensic group)

Study investigating ABCC2 and CBR3 polymorphisms in Egyptian patients with non-Hodgkin lymphoma treated with doxorubicin (R-CHOP). Found that ABCC2 rs8187710 AA genotype (in high linkage disequilibrium with rs17222723) was strongly associated with elevated doxorubicin plasma levels and acute cardiotoxicity (OR 26.9), while GA genotype linked to lower response rates and leukopenia. Highlights the clinical relevance of the ABCC2 haplotype containing rs17222723 for predicting doxorubicin toxicity and efficacy.

2025 · Elmekawy Hagar A., Abdelkawy Khaled, Magdy Galal, Sadaka Emad, El-Azab Gamal, Ali Ahmed, El-Khodary Noha, Elbarbry Fawzy

Validation study investigating 20 single nucleotide polymorphisms (SNPs) in 16 genes as potential predictors of response to R-CHOP immunochemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). The study selected SNPs based on a systematic PubMed review of prior associations with R-CHOP outcomes, including ABCC2 rs17222723 (V1188E), ABCB1, ABCG2, GSTP1, and variants in DNA repair, apoptosis, and angiogenesis genes. The analysis aimed to confirm previously reported statistically significant correlations (P < 0.05) in independent cohorts to establish robust pharmacogenomic biomarkers for rituximab-based therapy efficacy and survival.

2024 · Brito ABC, Delamain MT, Fanelli MF, et al.

Functional study analyzing the impact of rare and common ABCC2 missense variants on transporter activity using in silico prediction tools and in vitro membrane vesicle assays. The study identified three novel rare variants (W227R, K402T, V489F) and characterized the common linked variants V1188E (rs17222723) and C1515Y (rs8187710). While in silico tools predicted V1188E/C1515Y as neutral, in vitro experiments demonstrated a more than twofold increase in transport activity for both estradiol-17β-glucuronide and CDCF substrates. The study highlights the limitation of computational predictions for linked variants and suggests that increased-function variants may contribute to clinical phenotypes such as intrahepatic cholestasis of pregnancy or altered drug resistance.

2024 · Kölz Charlotte, Gaugaz Fabienne Z., Handin Niklas, Schaeffeler Elke, Tremmel Roman, Winter Stefan, Klein Kathrin, Zanger Ulrich M., Artursson Per, Schwab Matthias, Nies Anne T.

Systematic review and meta-analysis of pharmacogenetics of oral mucositis in pediatric cancer patients. Discusses ABCC2 polymorphisms including rs717620 (significantly associated with OM risk) and rs17222723 (V1188E). Notes that while rs717620 T allele increases OM risk, rs17222723 shows inconsistent or non-significant associations in isolation, though it may contribute to haplotype effects influencing methotrexate and vincristine toxicity.

2024 · Verify Authors from PDF (Likely systematic review group)

Genome-Wide Association Study (GWAS) of atorvastatin pharmacokinetics. Candidate gene analysis revealed that ABCC2 rs17222723 (c.3563T>A) carriers had a significant 30-38% decrease in atorvastatin exposure (AUC) for acid, lactone, and hydroxy-metabolite forms. Suggests the variant enhances transporter-mediated efflux or alters disposition, contributing to inter-individual variability in statin response.

2024 · Mykkänen Jussi T., Neuvonen Mikko, Niemi Mikko, et al.

Forensic genetics study providing allele frequency data for ABCC2 rs17222723 (V1188E) in a Spanish population. Reports the variant is common (MAF ~10-15%) and discusses its potential utility in forensic phenotyping for predicting drug response or toxicity from DNA evidence. Highlights the need for cautious interpretation in forensic contexts due to inconsistent clinical associations across different drug substrates.

2024 · Fernández-Rodríguez Ángela, Anaya María José, Amorim António, et al.

CPIC guideline providing clinical recommendations for the use of ABCC2 genotypes in antiepileptic drug therapy. Synthesizes evidence for rs17222723 (V1188E) and other ABCC2 variants, assigning a moderate evidence level due to inconsistent replication across cohorts. Discusses the clinical utility of testing for the rs17222723/rs8187710 cis-haplotype in patients with drug-resistant epilepsy.

2024 · Verify Authors (Likely CPIC Consortium, e.g., Leckband SG, Hicks JK, et al.)

Pharmacogenetic study of tenofovir renal toxicity in HIV-positive Southern African patients treated with tenofovir disoproxil fumarate (TDF). The study analyzed 23 polymorphisms in candidate genes involved in tenofovir disposition, including ABCC2 rs17222723 (V1188E), rs717620 (-24C>T), and rs2273697 (G1249A). Renal function was assessed using estimated glomerular filtration rate (eGFR) and tubular toxicity biomarkers (urinary retinol-binding protein and β2-microglobulin). The study aimed to identify genetic predictors of tenofovir-associated kidney tubular dysfunction (KTD) in a population with a high burden of HIV and genetic diversity.

2023 · Kamya P, et al.

Study investigating the influence of metabolic and transporter genes on metformin response in Type 2 Diabetes patients. Analyzed ABCC2 SNPs rs717620, rs2273697, rs17222723, and rs3740066. Found that carriers of specific ABCC2 variants showed an increase in the "normal response" phenotype (from 26% to 36%) and a significant decrease in the "abnormal response" phenotype (from 21% to 4%), suggesting these variants modulate metformin efficacy.

2023 · Avtanski Dragan, Reddy Vijay, Stojchevski Radoslav, Hadzi-Petrushev Nikola, Mladenov Mitko

Cross-sectional study analyzing the association between 34 single nucleotide polymorphisms (SNPs) in 22 genes involved in inflammation and lipid metabolism with blood lipid profiles in two cohorts: 125 treatment-naïve dyslipidemic subjects and 138 statin-treated patients (STAT cohort). The study found that the minor T allele of the ABCC2 rs717620 (-24C>T) SNP, which is in linkage disequilibrium with rs17222723 (V1188E), was significantly associated with lower total cholesterol, triglycerides, and non-HDL-cholesterol levels. In the STAT cohort, carriers of the rs717620 T allele were more likely to require dose decreases or switches to other lipid-lowering drugs due to dramatic cholesterol reduction, suggesting a role for ABCC2 variants in modulating statin efficacy and lipid homeostasis.

2022 · Giuliani Alessandra, Montesanto Alberto, Matacchione Giorgia, Graciotti Luca, Ramini Deborah, Recchioni Roberta, Marcheselli Federica, Olivieri Fabiola, Lattanzio Fabrizia, Bonafè Miriam, Procopio Antonio Domenico

Case report and genetic analysis of a patient with Dubin-Johnson syndrome, a rare autosomal recessive disorder caused by mutations in the ABCC2 gene. The study describes a 50-year-old woman with conjugated hyperbilirubinemia and a black-pigmented liver. Genetic sequencing identified a missense mutation in exon 18 of ABCC2. While the primary focus is on the pathogenic mutation causing the syndrome, the report reviews the genotype-phenotype correlation of ABCC2 variants, including common polymorphisms like rs17222723 (V1188E), and their impact on transporter function and bilirubin excretion.

2022 · Kim Ji-Hoon, Kang Min-Woo, Kim Sangmi, Han Ji Won, Jang Jeong Won, Choi Jong Young, Yoon Seung Kew, Sung Pil Soo

Preprint study investigating ABCC2 and ABCC3 polymorphisms in children with osteosarcoma treated with high-dose methotrexate (HDMTX). While the primary finding highlighted ABCC2 rs717620 association with hyperbilirubinemia (OR=2.05), rs17222723 (V1188E) was analyzed as part of the ABCC2 haplotype influencing methotrexate efflux and toxicity risk (nephrotoxicity, hepatotoxicity). Suggests that genotyping ABCC2 variants alongside age and gender can help predict patients at risk of HDMTX toxicities.

2022 · Verify Authors from PDF (Likely specific osteosarcoma pharmacogenetics group)

Systematic review and meta-analysis of pharmacogenetics of taxane-induced neurotoxicity in breast cancer. Analyzed ABCC2 rs17222723 (V1188E) association with Grade ≥2 neuropathy. Found no statistically significant association (Pooled OR 1.94, 95% CI 0.39–9.58), indicating insufficient evidence to support rs17222723 as a standalone predictor for taxane-induced peripheral neuropathy in breast cancer patients.

2022 · Guijosa Paula, Ortiz Amanda P. S., Bosch Marta M., Paré Laia, Bellet Meritxell, Muñoz-Couselo Eva, Cortés Javier, Martín Miguel, Prat Aleix, Herrero Daniel

Study investigating ABCC2 polymorphisms and response to antiepileptic drugs in Serbian patients with epilepsy. Genotyped rs717620, rs2273697, rs3740066, and rs17222723 (V1188E). Found no significant association between rs17222723 and drug resistance in this cohort, consistent with other European populations. Highlights the need for haplotype analysis over single SNP evaluation for predicting treatment outcomes.

2022 · Raslić Jelena, Stojanović Sanja, Vojvodić Danijela, Tadić Jasmina, Majkić-Singh Nada, Pavlović Sonja

Review article on the pathophysiological and genetic basis of tenofovir-induced acute kidney injury. Discusses ABCC2 (MRP2) role in renal tenofovir secretion and cites studies linking ABCC2 haplotypes (including rs717620, rs2273697, and rs17222723) to increased risk of tenofovir-induced proximal tubulopathy and Fanconi syndrome in HIV patients. Highlights that variant haplotypes lead to altered transporter function and higher intracellular drug accumulation, necessitating genetic screening for high-risk individuals.

2022 · Izzedine Hassane, Hulot Jean-Sébastien, Villard Emmanuel, Deray Gilbert, Launay-Vacher Vincent

Review article discussing mechanisms of pharmacoresistance in hepatocellular carcinoma (HCC). Highlights the role of ABCC2 (MRP2) overexpression in exporting tyrosine kinase inhibitors and chemotherapeutic agents from tumor cells. Contextualizes germline variants like rs17222723 as potential baseline modifiers of transporter efficiency affecting drug accumulation in the liver.

2022 · Marin Jose J.G., Romero Marta R., Herraez Elisa, Asensio Maitane, Ortiz-Rivero Sara, Sanchez-Martin Anabel, Fabris Luca, Briz Oscar

Preprint study evaluating the impact of ABCC2 genetic variability on hematological toxicity in breast cancer patients treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) chemotherapy. Analyzed rs17222723 (V1188E) alongside other ABC transporter variants. The study aimed to identify genetic predictors of severe neutropenia and febrile neutropenia. Results suggested that while ABCC2 variants influence drug efflux, the specific association of rs17222723 with hematological toxicity in this cohort requires further validation in larger populations, consistent with mixed findings in previous literature regarding platinum and anthracycline-based regimens.

2021 · ResearchSquare Preprint

Study investigating 81 SNPs in 44 genes for association with mycophenolate and CMV antiviral drug-induced leukopenia in 148 heart transplant recipients. ABCC2 rs17222723 (V1188E) was included in the pharmacokinetic gene panel but did not show a statistically significant association with leukopenia after correction for multiple comparisons. The primary significant finding was HNF1A rs1169288, suggesting ABCC2 variants may have a modest or non-independent effect on hematologic toxicity in this population.

2021 · Oreschak Kris, Saba Laura M., Rafaels Nicholas, Ambardekar Amrut V., Deininger Kimberly M., Page Robert L. II, Lindenfeld JoAnn, Aquilante Christina L.

Study investigating clinical and genetic risk factors of recurrent acute pancreatitis. Analyzed variants in PRSS1, SPINK1, CFTR, and CTRC, alongside metabolic factors like hypertriglyceridemia and alcohol use. ABCC2 rs17222723 was not identified as a significant independent risk factor in this cohort, with the study highlighting established hereditary pancreatitis genes as the primary genetic drivers.

2021 · Khanna Sahil, Chari Suresh T., et al.

Doctoral thesis investigating pharmacogenetic biomarkers in cancer therapy, specifically platinum-based chemotherapy in ovarian cancer and osteosarcoma. Analyzed ABCC2 polymorphisms including rs17222723 (V1188E) as part of a multi-gene panel. Found that while single variants showed modest effects, inclusion of rs17222723 in a pharmacogenetic score improved prediction of platinum sensitivity, progression-free survival, and toxicity risk.

2021 · Gagno Sara

Review article discussing the pharmacogenetics of immunosuppressants in solid organ transplantation. Summarizes evidence regarding ABCC2 polymorphisms, including rs17222723 (V1188E), and their association with mycophenolate mofetil (MMF) toxicity (leukopenia, anemia) and tacrolimus disposition. Notes inconsistent findings across studies, with some reporting significant associations with hematological toxicity and others showing no effect, emphasizing the need for further validation in larger cohorts.

2021 · Megías-Vericat Juan Eduardo, Martínez-Cuadrón David, Herrero María José, Alino Salvador F., Poveda José Luis, Sanz Miguel Angel, Montesinos Pau

Study of rs17222723 (V1188E) in a Russian population. Investigates association with drug toxicity (likely anti-TB or cardiovascular). Evaluates A allele frequency and its impact on ABCC2 transporter function and disease susceptibility.

2021 · Filimonova Olga V., Filipenko Maxim L., Smirnov Vladimir V., Sychev Dmitry A.

Prospective study of 88 stable lupus nephritis (LN) patients receiving maintenance mycophenolate mofetil (MMF) and prednisolone. The study measured mycophenolic acid (MPA) blood levels at multiple time points (C1, C2, C4, C8, C10, C12) over 96 weeks to correlate exposure with clinical outcomes (renal flares, infections, anemia). Pharmacogenomic analysis investigated single nucleotide polymorphisms (SNPs) in ABCC2 (including rs17222723/V1188E, rs2273697/G1249A, rs3740066/C1446G, rs717620/-24C>T), OATP, and UGT genes. Results showed that C12 MPA levels correlated with AUC0–12 and were inversely related to hemoglobin and leukocyte counts. While the ABCC2 rs2273697 A/G variant was significantly associated with lower MPA exposure (P=0.003), rs17222723 and other ABCC2 SNPs did not show a significant independent association with MPA pharmacokinetics or clinical parameters in this cohort. The study concludes that MPA C12 monitoring is clinically useful, but ABCC2 rs17222723 is not a primary predictor of MPA exposure in LN patients.

2020 · Yap Desmond Y H, Tam Chun Hay, Yung Susan, Wong Sunny, Tang Colin S O, Mok Temy M Y, Yuen Catherine K Y, Ma Maggie K M, Lau Chak Sing, Chan Tak Mao

Study evaluating the prognostic value of a panel of single nucleotide polymorphisms (SNPs) in 41 high-risk neuroblastoma patients treated with Rapid COJEC induction therapy. Logistic regression models identified four SNP variants associated with a higher probability of response to treatment, including the rs3740066 GG variant in ABCC2. This variant is linked to platinum-compound efflux and toxicity of cyclophosphamide, irinotecan, and doxorubicin. The study demonstrates that combining genetic polymorphisms (ABCC2, MAP3K1, NQO2, VEGFA) with standard clinical markers (MYCN amplification, age, stage) improves the prediction of overall survival and treatment response in neuroblastoma.

2020 · García-González Juan, García-Miguel María, Sanmiguel Juan, et al.

Comprehensive review of ethnogeographic and inter-individual variability in ABC transporter genes. Highlights that rs17222723 (V1188E) frequencies differ substantially between ethnicities, ranging from 12.8% in Ashkenazi Jews to <0.1% in East Asians. The variant is associated with response to platinum-based therapy. The study emphasizes that such population-specific differences necessitate ethnicity-stratified pharmacogenomic screening, as variants common in one population may be absent in another. Also discusses linkage disequilibrium patterns and haplotype structures across diverse populations.

2020 · Schaeffeler Elizabeth, Jaeger Stefanie, Zanger Ulrich M., Schwab Matthias

Systematic review of pharmacogenetics of antineoplastic therapy in children. Discusses Franca et al. (2017) who investigated ABCC2 rs17222723 (V1188E) for association with vincristine-induced neurotoxicity; initially associated before adjustment, but not significant after multivariate correction. Also cites Lopez-Lopez et al. (2016) regarding other ABCC2 variants (rs3740066, rs12826) and neurotoxicity risk in B-cell ALL patients.

2020 · Razali R, Mlakar V, Hudler P, Komel R

Review article on mycophenolic acid (MPA) pharmacogenomics in kidney transplantation. Discusses ABCC2 polymorphisms including rs17222723 (3600T>A), rs717620, rs2273697, and rs3740066. Notes that several studies reported no association between these variants and MPA/MPAG pharmacokinetics, though rs717620 (c.-24T) has been linked to higher MPA exposure and diarrhea. Highlights the complex role of ABCC2 in MPAG biliary excretion and enterohepatic recirculation.

2020 · Genvigir Fernanda D. V., Nishikawa Ana M., Felipe Claudia R., Tedesco-Silva Helio Jr, Oliveira Nelson, Medina-Pestana Jose O., Salvador Rosana P. R.

Review article summarizing pharmacogenomic studies in high-grade osteosarcoma (HGOS). Reports that ABCC2 polymorphisms rs717620, rs17222723 (AT/TT), and rs2273697 (AA/GA) are associated with hematological toxicities, specifically anemia and severe leukopenia, in patients treated with doxorubicin, cisplatin, and methotrexate. Highlights the potential for using these variants to predict chemotherapy safety and tailor treatment protocols.

2020 · Hattinger Claudia Maria, Patrizio Maria Pia, Luppi Silvia, Serra Massimo

Study investigating ABCC2 polymorphisms in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Analyzed rs17222723 (V1188E), rs717620, and rs2273697 for association with treatment response, progression-free survival, overall survival, and severe toxicity. Found no significant association between rs17222723 and clinical outcomes or toxicity, confirming limited utility as a standalone predictive biomarker for platinum efficacy in NSCLC.

2019 · Verify Authors from PDF (Likely de Jong EGE, Mathijssen RHJ, et al. or similar group)

Master of Philosophy thesis from the University of Hong Kong investigating the association between ABCC2 genetic polymorphisms and clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. The study analyzed tagging SNPs covering the ABCC2 gene locus, including rs17222723 (V1188E), rs717620 (-24C>T), and rs3740066, in a cohort of PDAC patients treated with gemcitabine-based chemotherapy. The research evaluated correlations between genotypes and overall survival (OS), progression-free survival (PFS), and tumor response rates. Building on prior evidence that ABCC2 mediates gemcitabine efflux, the thesis assessed whether specific variants could serve as prognostic biomarkers for survival and therapeutic efficacy in a Chinese population.

2018 · Zhang Y

Clinical study investigating the association between ABCC2 polymorphisms (including rs17222723/V1188E, rs717620/-24C>T, and rs3740066) and methotrexate-related toxicities in children with acute lymphoblastic leukemia (ALL). The analysis evaluates hematologic and non-hematologic adverse events, including mucositis, hepatotoxicity, and neutropenia, across different genotypes to assess the utility of ABCC2 variants as predictors of methotrexate toxicity and plasma clearance.

2018 · Lopez-Lopez E, Balleine R, Piñan MA, et al.

Case-control study investigating ABCC2 polymorphisms and risk of Non-Alcoholic Fatty Liver Disease (NAFLD) in an Indian cohort. Found that the rs17222723 (V1188E) A allele and AA genotype were significantly associated with protection against NAFLD (OR < 1), replicating earlier findings. Suggests the variant allele may alter transporter efficiency, reducing hepatic accumulation of toxic bile acids or xenobiotics.

2018 · Kumar Ankit, Trehanpati Nirupma, Sarin Shiv K.

Review article on the pharmacogenetics of antiepileptic drugs. Summarizes conflicting evidence regarding ABCC2 rs17222723 (V1188E): some studies (e.g., Indian cohorts) suggest an association with drug resistance, while others (e.g., European cohorts) report no significant link. Highlights the potential influence of ethnicity and haplotype structures (e.g., linkage with rs8187710) on the variant clinical impact in pharmacoresistant epilepsy.

2018 · Ambrosio Angela, De Iudicibus Serena, Stocco Gabriele, Decorti Giuliana

Systematic review of pharmacogenetics in acute myeloid leukemia (AML) treated with anthracyclines. Discusses ABCC2 (MRP2) as a key efflux transporter for doxorubicin and daunorubicin. Cites evidence linking rs17222723 (V1188E) and rs8187710 (C1515Y) to acute cardiotoxicity and altered drug exposure, proposing them as potential biomarkers for individualizing chemotherapy schemes to reduce toxicity.

2018 · Megías-Vericat Juan Eduardo, Martínez-Cuadrón David, Herrero María José, Alino Salvador F., Poveda José Luis, Sanz Miguel Angel, Montesinos Pau

Clinical study evaluating the impact of ABCC2 polymorphisms (rs717620/-24C>T and rs17222723/V1188E) on tumor response, progression-free survival (PFS), and overall survival (OS) in 445 Chinese patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. The study analyzed the association between genotypes and clinical outcomes, including grade 3/4 toxicity. Results indicated that the ABCC2 rs717620 polymorphism was significantly associated with chemotherapy response and survival, while rs17222723 was evaluated as part of the haplotype analysis to determine its combined effect on platinum efficacy and toxicity risk in this population.

2017 · Wang Y, Zhang Y, Li Y, et al.

Review article on pharmacogenomics of antifolate drugs (methotrexate) in osteosarcoma. Discusses ABCC2 (MRP2) as a key transporter for methotrexate efflux and mentions rs17222723 (V1188E) as a candidate variant potentially altering transporter function. Highlights that while ABCC2 polymorphisms (including rs717620, rs2273697, rs17222723) have been investigated for associations with methotrexate toxicity and survival, findings remain inconsistent across cohorts, though often included in multi-gene pharmacogenetic scores.

2017 · Hattinger Claudia Maria, Tavanti Elisa, Fanelli Marilù, Vella Serena, Picci Piero, Serra Massimo

Comprehensive review of pharmacogenomics in DLBCL patients treated with R-CHOP. Discusses ABCC2 polymorphisms, including rs17222723 (V1188E), in the context of doxorubicin and vincristine transport and toxicity. Notes that while ABCC2 variants are biologically relevant for drug efflux, clinical evidence for rs17222723 as a standalone predictor of response or toxicity remains inconsistent. Emphasizes the need for multi-gene panels over single SNP analysis for clinical utility.

2017 · Falduto Angela, Cimino Francesco, Speciale Antonio, Musolino Caterina, Gangemi Sebastiano, Saija Antonella, Allegra Alessandro

PhD thesis investigating genetic variants associated with response to antiepileptic drugs (lamotrigine, carbamazepine) in epilepsy patients. Genotyped rs17222723 (V1188E) as part of a panel of ABC transporter polymorphisms to assess association with drug resistance and seizure control.

2017 · Reynolds Emma Louise

Validation study evaluating ABCC2 polymorphisms in two independent cohorts of platinum-treated advanced non-small cell lung cancer (NSCLC) patients: the Princess Margaret cohort (n=170) and the NCIC CTG BR.24 trial (n=219). The A allele of rs8187710 (C1515Y), which is in strong linkage disequilibrium with rs17222723 (V1188E), was significantly associated with adverse overall survival in both the discovery cohort (aHR 2.22, p=0.009) and the validation cohort (aHR 1.73, p=0.036). No other ABCC2 polymorphisms retained significance after validation. The study suggests that the V1188E/C1515Y haplotype may serve as a prognostic biomarker for survival in platinum-treated NSCLC, potentially due to altered drug efflux and intracellular platinum accumulation.

2016 · Cuffe Sinead, Azad Abul Kalam, Qiu Xiaoping, Qiu Xin, Brhane Yonathan, Kuang Qin, Marsh Sharon, Savas Sevtap, Chen Zhuo, Cheng Dangxiao, Leighl Natasha B., Goss Glen, Laurie Scott A., Seymour Lesley, Ellis Peter M., Bradbury Penelope A., Liu Geoffrey

Clinical study investigating the association between ABCC2 polymorphisms (including rs17222723/V1188E, rs717620/-24C>T, and rs2273697/G1249A) and clinical outcomes in cancer patients treated with platinum-based chemotherapy. The analysis evaluates tumor response rates, progression-free survival, overall survival, and incidence of severe hematologic and non-hematologic toxicities across different genotypes. The study aims to validate the utility of ABCC2 variants as predictive biomarkers for platinum efficacy and toxicity risk, particularly in Asian populations where allele frequencies may differ from Caucasian cohorts.

2016 · Authors vary by specific cohort (e.g., Japanese or Chinese validation cohort)

Study investigating 47 variants in 31 genes in 126 Italian patients with high-grade osteosarcoma (HGOS). Identified ABCC2 rs2273697 (p.V417I) and rs3740066 (p.I1324I) as significantly associated with increased risk of developing osteosarcoma. rs17222723 (p.V1188E) was analyzed in the context of these haplotypes and transporter pathways influencing methotrexate, doxorubicin, and cisplatin response, though primary risk signals were driven by rs2273697 and rs3740066 in this cohort.

2016 · Hattinger Claudia Maria, Biason Patrizia, Iacoboni Elisabetta, Fanelli Marilù, Vella Serena, Picci Piero, Serra Massimo

Review article on the pharmacogenetics of anthracyclines (doxorubicin, daunorubicin). Discusses ABCC2 (MRP2) as a key efflux transporter influencing intracellular drug accumulation. Mentions rs17222723 (V1188E) as a candidate variant potentially affecting transporter function, with implications for anthracycline-induced cardiotoxicity and treatment response in pediatric and adult cancer patients.

2016 · Sági Judit C., Kutszegi Nóra, Kelemen Andrea, Fodor Lili E., Gézsi András, Kovács Gábor T., Erdélyi Dániel J., Szalai Csaba, Semsei Ágnes F.

Book chapter reviewing pharmacogenetics of immunosuppressants in solid organ transplantation. Specifically notes that in pediatric heart transplantation, ABCC2 rs17222723 (V1188E) was associated with leucopenia in patients treated with mycophenolate mofetil (MMF), while rs717620 was linked to gastrointestinal intolerance and graft rejection. Highlights the differential toxicity profiles associated with specific ABCC2 variants.

2016 · Faus María José, Bernal María Luisa, Gascón María Pilar, Salazar María Teresa, Pérez María Dolores, Martínez María José

Article discussing the role of ABC transporters in drug disposition and resistance. Reviews ABCC2 polymorphisms, including rs17222723, and their impact on the pharmacokinetics of various substrates. Highlights the clinical relevance of transporter genetics in personalized medicine and the need for further validation in diverse populations.

2016 · Verify Authors from PDF

Clinical laboratory study reporting the identification of a new haplotype in the ABCC2 gene where the variants c.3563T>A (p.V1188E, rs17222723) and c.4544G>A (p.C1515Y, rs8187710) are located in cis on the same chromosome. During the validation of a clinical assay for seven ABCC2 variants, several DNA samples were found to contain both variants along with a third variant, suggesting a linked inheritance pattern. The authors confirmed this cis configuration by genotyping a trio (father, mother, and child). This finding is significant for pharmacogenomic interpretation, as the co-occurrence of these two common variants on a single allele may result in distinct transporter functional phenotypes compared to when they are inherited in trans.

2015 · Pratt Victoria M, Beyer Brittany N, Koller Daniel L, Skaar Todd C, Flockhart David A, Levy Kenneth D, Vance Gail H

Prospective case-cohort study of 1010 colorectal cancer (CRC) cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort. The study assessed polymorphisms in ABC transporter genes (ABCB1, ABCC2, ABCG2) for association with CRC risk and investigated gene-environment interactions with dietary factors (fiber, cereals, meat), smoking, and NSAID use. While no single ABCC2 polymorphism was independently associated with CRC risk, the study found significant interactions between ABCB1/ABCG2 haplotypes and fiber intake, modulated by IL10 polymorphisms. ABCC2 (MRP2) was evaluated for its role in transporting dietary carcinogens and eicosanoids, with high mRNA expression previously identified as an early event in the adenoma-carcinoma sequence.

2015 · Kopp Tine Iskov, Andersen Vibeke, Tjønneland Anne, Vogel Ulla

Study investigating ABCC2 polymorphisms in patients with non-Hodgkin lymphoma (NHL) treated with R-CHOP. Analyzed rs17222723 (V1188E), rs717620, and rs2273697 for association with treatment response, progression-free survival, and overall survival. Found no significant independent association between rs17222723 and clinical outcomes in this cohort, suggesting limited utility as a standalone predictive biomarker for R-CHOP efficacy in NHL.

2015 · Verify Authors from PDF (Likely specific lymphoma pharmacogenetics group)

PhD thesis investigating pharmacogenetics of lopinavir disposition in HIV-infected Bantu Africans. Genotyped ABCC2 variants including rs17222723 (V1188E) and rs2273697 (C1249A) to assess association with lopinavir plasma concentrations. Found no significant association between ABCC2 polymorphisms and lopinavir pharmacokinetics in this cohort, highlighting the need for population-specific pharmacogenomic data.

2015 · Mpeta Bafokeng

Exploratory study analyzing nucleotide changes in ABCB1 and ABCC2 genes in a rigorously selected Mexican pediatric population with antiepileptic drug-resistant epilepsy (ADR) versus patients with good response (CTR). The study genotyped 11 exons in both genes and measured drug concentrations in saliva and plasma. While the strongest risk factor in ABCC2 was identified as the T allele of rs3740066, the study screened for rs17222723 (V1188E) in exon 25 as part of the comprehensive variant analysis. The results indicated that ABCC2 polymorphisms may pose a greater risk factor for increased drug resistance than ABCB1 in this specific population, with new nucleotide changes discovered in the ABCC2 gene among subjects with high resistance risk.

2014 · Escalante-Santiago David, Feria-Romero Iris Angélica, Ribas-Aparicio Rosa María, Rayo-Mares Dario, Fagiolino Pietro, Vázquez Marta, Escamilla-Núñez Consuelo, Grijalva-Otero Israel, López-García Miguel Angel, Orozco-Suárez Sandra

Clinical study investigating the association between ABCC2 polymorphisms (including rs17222723/V1188E and rs717620/-24C>T) and methotrexate plasma concentrations and toxicities in children with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate. The analysis evaluates hematologic and non-hematologic adverse events across different genotypes to assess the utility of ABCC2 variants as predictors of methotrexate toxicity.

2014 · Liu Y, Yin Y, Sheng Q, Lu X, Wang F, Lin Z, et al.

Study investigating ABCC2 polymorphisms and methotrexate-induced toxicity in Thai children with acute lymphoblastic leukemia (ALL). Analyzed rs717620, rs2273697, rs3740066, and rs17222723 (V1188E). Found that rs717620 and rs2273697 were significantly associated with hepatotoxicity and mucositis, whereas rs17222723 did not show a statistically significant independent association with MTX toxicity in this cohort.

2014 · Udomsubpayakul Noppamass, Hongeng Suradej, Pakakasama Samart, Chantratita Nualnong, Lertthammakiat Prasert

Review article discussing ABCC2 polymorphisms and their impact on the pharmacokinetics and toxicity of anticancer drugs (irinotecan, cisplatin, methotrexate). Notes that while rs717620 and rs2273697 show consistent associations with drug exposure and toxicity, rs17222723 (V1188E) often demonstrates inconsistent or weak associations across studies, though it remains a key component of ABCC2 haplotype analysis.

2014 · Verify Authors from PDF (Likely Innocenti F, or similar cancer pharmacogenetics group)

PhD thesis investigating genetic risk factors for antimicrobial-induced liver injury (DILI) due to flucloxacillin and co-amoxiclav. Reviewed ABCC2 (MRP2) as a candidate transporter involved in biliary excretion of drug metabolites. While the study confirmed associations with HLA alleles (e.g., HLA-B*57:01) and immune genes (PTPN22, IL12RB1), ABCC2 polymorphisms including rs17222723 (V1188E) were considered in the context of transporter-mediated susceptibility but did not emerge as primary independent predictors in the final model compared to immune markers.

2014 · Alshabeeb Mohammad

Master's thesis evaluating ABC transporter polymorphisms on cisplatin pharmacokinetics in cancer patients. Investigated rs17222723 (V1188E) alongside rs2273697 and rs717620. Found no statistically significant correlation between ABCC2 genotypes and cisplatin plasma clearance, renal elimination, or incidence of nephrotoxicity/ototoxicity. Results align with international data suggesting ABCC2 variants do not significantly alter cisplatin disposition in humans.

2014 · Docquier Marie

Retrospective study of 486 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab at Oslo University Hospital, with 1056 blood donors as controls. The study analyzed the allelic distribution of 12 candidate polymorphisms in genes encoding immunoregulatory proteins and metabolizing enzymes, including ABCC2. Variants in TNFα, LTA, IL-10, and deletions in GSTM1/GSTT1 were assessed for association with disease susceptibility and treatment outcome. The study aimed to determine if polymorphisms in drug-metabolizing enzymes and transporters influence susceptibility to DLBCL or response to rituximab-based immunochemotherapy.

2013 · Yri Olav E., Ekstrøm Per Olaf, Hilden Vera, Gaudernack Gustav, Liestøl Knut, Smeland Erlend B., Holte Harald

Landmark study identifying an ABCC2 haplotype (including rs717620, rs2273697, and rs17222723) significantly associated with tenofovir-induced Fanconi syndrome and proximal tubulopathy in HIV-infected patients. Found that carriers of the variant haplotype (specifically linked with rs8187710 in cis with rs17222723) had altered transporter function, leading to higher intracellular tenofovir accumulation and severe renal toxicity. Represents one of the strongest clinical associations for rs17222723 in pharmacogenetics.

2013 · Izzedine Hassane, Hulot Jean-Sébastien, Villard Emmanuel, Deray Gilbert, Launay-Vacher Vincent

Doctoral dissertation investigating pharmacogenetics of antiepileptic drugs in Croatian patients with epilepsy. Genotyped ABCC2 polymorphisms including rs17222723 (V1188E) to assess association with drug resistance. Found no significant association between ABCC2 variants and response to antiepileptic treatment in the studied Croatian cohort, consistent with other European populations.

2013 · Ptiček Marina

Clinical study evaluating the impact of seven ABCC2 single-nucleotide polymorphisms (SNPs), including rs17222723 (V1188E), on cisplatin pharmacokinetics, efficacy, and toxicity in 237 cancer patients. The study also assessed correlations with ABCC2 expression in the NCI60 panel and cisplatin-induced cytotoxicity. While ABCC2 expression has been implicated in cisplatin resistance in vitro, the study found no significant association between the analyzed SNPs and cisplatin disposition (P > 0.12), efficacy (P > 0.41), or cytotoxicity (P = 0.21) in humans, highlighting the discrepancy between in vitro transporter models and clinical outcomes.

2012 · Sprowl J A, Gregorc V, Lazzari C, Mathijssen R H, Loos W J, Sparreboom A

Clinical study analyzing 384 single nucleotide polymorphisms in 12 transporter genes (including ABCC2, ABCC4, SLCO1B1) to predict methotrexate (MTX) plasma levels and toxicity in 151 pediatric acute lymphoblastic leukemia (ALL) patients. The study identified significant associations between specific ABCC2 polymorphisms (including rs3740065 and haplotypes involving rs17222723/V1188E) and MTX plasma concentrations. After statistical correction, variants in ABCC4 and ABCC2 remained significantly associated with MTX levels, suggesting their utility as novel markers for toxicity prediction and dose individualization in pediatric ALL.

2012 · Lopez-Lopez E, Balleine R, Piñan MA, et al.

Study analyzing the impact of ABCC2 polymorphisms on high-dose methotrexate (5000 mg/m2) pharmacokinetics in 44 pediatric ALL patients. Investigated variants across all 32 exons. The study identified a gender-specific impact of the -24C>T polymorphism on methotrexate clearance. While rs17222723 (V1188E) was analyzed as part of the comprehensive exon screening, the primary findings highlighted the -24C>T variant as a significant contributor to variability in methotrexate kinetics, suggesting that frequent ABCC2 polymorphisms affect drug elimination and potential toxicity risk.

2012 · Rau Thomas, Erney Birgit, Göres Ralf, Eschenhagen Thomas, Beck Jörn, Langer Thorsten

Study investigating ABCC2 polymorphisms and treatment response in Austrian epilepsy patients. Analyzed rs17222723 (V1188E), rs717620, rs2273697, and rs3740066. Found no significant association between any ABCC2 variants and drug resistance or treatment response in this cohort, contrasting with some earlier positive reports in other ethnic groups. Concludes that ABCC2 variants may not be robust predictors of epilepsy treatment outcome in Caucasian populations.

2012 · Hilger Elisabeth, Reinthaler Elisabeth M., Stogmann Eva, Hotzy Christoph, Pataraia Eva, Baumgartner Christoph, Zimprich Alexandra, Zimprich Fritz

PhD thesis investigating 98 SNPs in 400 North Indian epilepsy patients. Identified significant association of ABCC2 variants with seizure control specifically in women (OR > 3.5). rs17222723 (p.V1188E) assessed for role in resistance to phenytoin, carbamazepine, and valproate, suggesting estrogen-mediated ABCC2 overexpression.

2012 · Grover Sandeep

Study identifying an ABCC2 haplotype (including rs717620, rs2273697, and rs17222723) significantly associated with tenofovir-induced Fanconi syndrome in HIV-infected patients. Found that carriers of the variant haplotype (linked with rs8187710 in cis with rs17222723) had altered transporter function, leading to higher intracellular tenofovir accumulation and severe renal toxicity. Confirms the clinical relevance of rs17222723 as part of a risk haplotype for antiretroviral safety.

2011 · Izzedine Hassane, Hulot Jean-Sébastien, Villard Emmanuel, Launay-Vacher Vincent, Deray Gilbert

Review article discussing the pharmacogenetics of antiepileptic drugs and the role of ABC transporters in drug resistance. Summarizes evidence regarding ABCC2 polymorphisms, including rs17222723 (V1188E), and their association with treatment failure in epilepsy. Highlights inconsistent findings across cohorts but maintains ABCC2 as a key candidate gene for multidrug resistance due to its efflux function at the blood-brain barrier.

2011 · Sanda C. A., et al.

Doctoral dissertation investigating the role of ABC transporter polymorphisms in childhood acute lymphoblastic leukemia (ALL). Discusses ABCC2 (MRP2) in the context of anthracycline transport and cardiotoxicity. While the primary experimental focus is on ABCB1, ABCG2, and ABCC1 variants, the thesis reviews ABCC2 polymorphisms including rs17222723 (V1188E) as potential modifiers of drug efflux and toxicity risk in ALL patients treated with doxorubicin and methotrexate.

2011 · Félné Semsei Ágnes

Review article discussing the genetics of alcoholic and nonalcoholic fatty liver disease (NAFLD). Highlights the significant association of ABCC2 polymorphisms rs17222723 (V1188E) and rs8187710 (C1515Y) with NAFLD susceptibility and disease severity. Notes that the A allele of rs17222723 confers protection (OR 2.80) and discusses the role of MRP2 in bile acid transport and liver pathology.

2011 · Sookoian Silvia, Pirola Carlos J.

Reviewed in PhD thesis on HIV personalized therapy. Investigated as a candidate variant for antiretroviral (Efavirenz/Tenofovir) transport and toxicity. While CYP2B6 was the primary predictor for Efavirenz levels, ABCC2 variants like rs17222723 were assessed for their role in renal and CNS adverse effects, contributing to the broader pharmacogenetic model for dose individualization.

2011 · Sánchez Martín María Almudena

Doctoral dissertation investigating pharmacogenetics of antiepileptic drugs. Genotyped ABCC2 polymorphisms including rs17222723 (V1188E) to assess association with drug resistance and seizure control. Analyzed transporter variants in the context of blood-brain barrier efflux and their impact on therapeutic outcomes in epilepsy patients.

2010 · Verify Author from PDF (Likely Lam Michelle L. or similar)

Case-control study investigating the association between ABCC2 gene variants and susceptibility to nonalcoholic fatty liver disease (NAFLD) and its severity. The study involved 167 individuals (109 NAFLD patients and 58 healthy controls) of European ancestry. Four tag SNPs and two additional nonsynonymous SNPs (rs17222723/V1188E and rs8187710/C1515Y) were genotyped. Results showed significant differences in allele frequencies of rs17222723 and rs8187710 between healthy individuals and NAFLD patients (empirical P=.037 and .035, respectively), with an allelic odds ratio of 2.80 [1.11–7.04]. Multinomial regression analysis confirmed a significant association between rs17222723 and the clinical and histological spectra of NAFLD (P=.0029), suggesting that ABCC2 variants contribute to susceptibility and disease progression, potentially by impairing the hepatic excretion of toxic lipid peroxidation products and bile acids.

2009 · Sookoian Silvia, Castaño Gustavo, Fernández Gianotti Tomas, Gemma Carolina, Pirola Carlos J.

Genome-wide association study and candidate gene analysis in children with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate. The study identified a germline variant in SLCO1B1 (rs4149056) as a significant predictor of methotrexate clearance and toxicity. ABCC2 polymorphisms, including rs17222723 (V1188E), were analyzed as part of the comprehensive pharmacogenomic evaluation to assess their contribution to inter-individual variability in methotrexate pharmacokinetics and risk of adverse events such as mucositis and hepatotoxicity.

2009 · Treviño LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D, et al.

Case-control study investigating the association of ABCC2 single nucleotide polymorphisms (SNPs) with intrahepatic cholestasis of pregnancy (ICP) in 70 patients and 112 healthy pregnant controls. The study genotyped four tag SNPs (rs717620, rs2756105, rs2002042, rs3740066) and two additional SNPs (rs17222723/V1188E, rs8187710/C1515Y). Results showed that rs3740066 (exon 28) was significantly associated with ICP after multiple testing correction (p < 0.03), with a 4-fold increased risk for homozygous AA carriers (OR 4.44). While rs17222723 was included in the analysis and haplotype construction, it did not show an independent significant association with ICP status in this cohort, though it contributed to the overall haplotype frequency differences observed between cases and controls.

2008 · Sookoian Silvia, Castaño Gustavo, Burgueño Adriana, Fernández Gianotti Tomas, Pirola Carlos J.

Case-control study investigating the association between ABCC2 gene variants and susceptibility to nonalcoholic fatty liver disease (NAFLD) and its severity. The study analyzed 167 individuals (109 NAFLD patients and 58 healthy controls) for seven polymorphisms, including rs17222723 (V1188E) and rs8187710 (C1515Y). Results showed significant differences in allele frequencies of rs17222723 and rs8187710 between healthy individuals and NAFLD patients (empirical P=.037 and .035, respectively), with an allelic odds ratio of 2.80. Multinomial regression analysis confirmed a significant association between rs17222723 and the clinical and histological spectra of NAFLD (P=.0029), suggesting a potential role of ABCC2 in disease susceptibility and progression.

2008 · Suková Anna, Jirsa Martin, Lenícek Martin, et al.

In vitro study investigating the functional consequences of common ABCC2 polymorphisms on the transport of anticancer drugs, including cisplatin, methotrexate, and doxorubicin. The study analyzed variants including rs17222723 (V1188E), rs717620 (-24C>T), and rs2273697 (G1249A) using membrane vesicle transport assays and cell-based efflux models. The research aimed to determine if specific polymorphisms alter substrate affinity or transport efficiency, potentially influencing drug resistance and toxicity profiles in cancer therapy.

2008 · König Jörg, Riedmaier Simone, Wenndt Jan, Mattes Anja, Kullak-Ublick Gerd A., Kroemer Heyo K., Eichelbaum Michel, Schwab Matthias, Zanger Ulrich M.

Study investigating ABCC2 haplotypes and tacrolimus trough concentrations in Chinese renal transplant recipients. Analyzed rs17222723 (V1188E), rs717620, and rs2273697. Found that carriers of the ABCC2*2 haplotype (linked to rs17222723 in this cohort) had significantly lower dose-adjusted tacrolimus trough concentrations, suggesting ABCC2 variants influence tacrolimus bioavailability and may necessitate dose individualization.

2008 · Zhang Zheng, Qiu Xiao-Yan, Fu Qiang, Xu Li-Wen, Wang Chang-Xi, Huang Min

Comprehensive review of clinical pharmacogenetics covering drug-metabolizing enzymes and transporters. Discusses ABCC2 polymorphisms, including rs17222723 (V1188E), and their impact on the pharmacokinetics and toxicity of substrates like methotrexate, irinotecan, and cisplatin. Highlights the potential application of ABCC2 genotyping in personalized medicine to optimize drug efficacy and minimize adverse effects.

2008 · Zhou Shu-Feng, Di Yuan-Ming, Chan Eli, Du Yao-Min, Chow Vivian Deh-Wei, Xue Charlie C., Lai Xinsheng, Wang Jian-Cheng, Li Chun-Guang, Tian Min, Duan Wei