rs12777823

CYP2C9 metabolizes approximately 20% of clinically administered drugs. Several single-nucleotide polymorphisms (SNPs) of CYP2C9 (e.g., *2, *3, *8, and rs12777823) are used as biomarkers to predict CYP2C9 activity. However, a large proportion of variability in CYP2C9 expression remains unexplained. We previously identified a variable number tandem repeat (pVNTR) polymorphism in the CYP2C9 promoter. The short repeat (pVNTR-S) showed reduced transcriptional activity in reporter gene assays and was…

2025 · Montalvo AD, Gong Y, Collins JM et al.

Alleles in the VKORC1, CYP2C9, and CYP4F2 genes can influence Warfarin dose requirement. We aimed to determine the frequency of the polymorphisms in these genes in healthy individuals from Cali, Colombia. Observational study where total blood was collected from 107 healthy donors who attended a higher educational institution in Cali, Colombia. Sanger sequencing of exons 2, 3, 5, and 7 of the CYP2C9 gene; the common promoter region of CYP (rs12777823); exon 11 of CPY4F2 and the polymorphism c.-16…

2023 · Giraldo-Ocampo S, Diaz-Ordoñez L, Silva-Cuero YK et al.

Diversity in pharmacogenomic studies is poor, especially in relation to the inclusion of black African patients. Lack of funding and difficulties in recruitment, together with the requirement for large sample sizes because of the extensive genetic diversity in Africa, are amongst the factors which have hampered pharmacogenomic studies in Africa. Warfarin is widely used in sub-Saharan Africa, but as in other populations, dosing is highly variable due to genetic and non-genetic factors. In order t…

2022 · Asiimwe IG, Blockman M, Cohen K et al.

Pharmacogenetic testing is increasingly available from clinical and research laboratories. However, only a limited number of quality control and other reference materials are currently available for many of the variants that are tested. The Association for Molecular Pathology Pharmacogenetic Work Group has published a series of papers recommending alleles for inclusion in clinical testing. Several of the alleles were not considered for tier 1 because of a lack of reference materials. To address…

2021 · Pratt VM, Turner A, Broeckel U et al.

Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9…

2020 · Asiimwe IG, Zhang EJ, Osanlou R et al.

This study was designed to develop a high-resolution melting (HRM) analysis-based cardiovascular (CV) pharmacogenetics (PGx) genotyping panel for the Canon DNA Genetic Analyzer multiplex genotyping platform and cross-validate its performance with the TaqMan®-based OpenArray® method. The CV PGx genotyping panel containing 17 single nucleotide polymorphisms (SNPs) selected from 5 genes (CYP2C9, CYP2C19, CYP4F2, SLCO1B1, and VKORC1) and the CYP2C cluster was used to compare genotyping res…

2019 · Langaee T, El Rouby N, Stauffer L et al.

We aim to develop warfarin dosing algorithm for African-Americans. We explored demographic, clinical, and genetic data from a previously collected cohort of 163 African-American patients with a stable warfarin dose. We explored 2 approaches to develop the algorithm: multiple linear regression and artificial neural network (ANN). The clinical significance of the 2 dosing algorithms was evaluated by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actua…

2016 · Alzubiedi S, Saleh MI

Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by r…

2015 · Limdi NA, Brown TM, Yan Q et al.

VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin were obtained at I…

2013 · Perera MA, Cavallari LH, Limdi NA et al.

Clopidogrel therapy improves cardiovascular outcomes in patients with acute coronary syndromes and following percutaneous coronary intervention by inhibiting adenosine diphosphate (ADP)-dependent platelet activation. However, nonresponsiveness is widely recognized and is related to recurrent ischemic events. To identify gene variants that influence clopidogrel response. In the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study (2006-2008), we administered clopidogrel for 7 days to 429 he…

2009 · Shuldiner AR, O'Connell JR, Bliden KP et al.