Pharmacogenetics of warfarin dosing in patients of African and European ancestry

Author:

Shendre Aditi1,Dillon Chrisly2,Limdi Nita A2

Affiliation:

1. Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University Purdue University Indianapolis, IN 46202, USA

2. Department of Neurology, School of Medicine, University of Alabama at Birmingham, AL 35294, USA

Abstract

Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Observational studies have demonstrated the significant impact of single nucleotide polymorphisms in CYP2C9 and VKORC1 on warfarin dose in patients of European ancestry and African–Americans. This evidence supported the design and conduct of clinical trials to assess whether genotype-guided dosing results in improved anticoagulation control and outcomes. The trial results have shown discordance by race, with pharmacogenetic algorithms improving dose and anticoagulation control among European ancestry patients compared with African–American patients. Herein, we review the evidence from observational and interventional studies, highlight the need for inclusion of minority race groups and propose the need to develop race specific dosing algorithms.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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