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Scholars Research Library

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Der Pharmacia Lettre

Abstract

Informative SNPs associated with warfarin dose requirement in ethnically diverse population

Author(s): Nima Patel-Shori, Anurag Mishra, Mispa Ajua-Alemanji, Edlira Hoxha, Katsiarina Bykov, Michael R. Jacobs, Patrick McDonnell, John P. Gaughan, Ronald Rubin, John Woodward, Evgeny Krynetskiy

Genetic polymorphisms in genes coding for warfarin-metabolizing, -transporting, and target proteins represent risk factors, which account for the significant part of the variability in warfarin-based anticoagulation therapy. Because warfarin dose requirement is a polygenic trait, the existing algorithms have limited capacity to predict warfarin dose. The goal of this retrospective study was to assess the effects of genetic polymorphisms in candidate genes on warfarin dose requirement in ethnically diverse population. We performed genotyping and statistical analysis of association between genotype and warfarin dose, or adverse drug event (bleeding) in 60 patients from three ethnic groups (African Americans, Caucasians, and Hispanics) under stable anti-coagulation with warfarin. Warfarin dose was significantly different among ethnic groups, with highest in African Americans and lowest in Hispanics, in parallel with inter-ethnic frequencies of allelic variants of VKORC1 and GGCX genes. The strongest predictors of the dose in stable patients were age (p<0.0001) and VKORC1 haplotype (p<0.0001). Our results showed that single nucleotide polymorphisms (SNPs) in GGCX, CYP2C9, and VKORC1 genes were useful biomarkers for warfarin dose requirement in an ethnically diverse population. Warfarin dose for the carriers of VKORC1*2 allele was significantly lower (5.45?±1.82 vs. 2.98?±1.09 mg/day; P=0.0069) in Caucasians but not in two other population groups, suggesting that the same SNPs may have different effects depending on the genetic context.
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