Pharmacogenomics of warfarin: uncovering a piece of the warfarin mystery

American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists
Michael P GulsethWilliam E Dager

Abstract

The literature on the pharmacogenomics of warfarin and the use of genetic testing to optimize initial and maintenance warfarin dosing is reviewed. Warfarin tablets contain a racemic mixture of R- and S-isomers. The S-isomer is responsible for about 70% of warfarin's anticoagulant effect. Cytochrome P-450 isoenzyme 2C9 (CYP2C9) metabolizes S-warfarin into two inactive metabolites. Genetic variations to the gene encoding CYP2C9 (CYP2C9 ) are known to affect warfarin clearance. Single nucleotide polymorphisms (SNPs) have been identified that clearly influence warfarin metabolism and sensitivity, including SNP variants of CYP2C9 and SNPs in vitamin K epoxide reductase complex subunit 1 (VKORC1), which influence an individual's sensitivity to a given dose. Retrospective studies have evaluated potential factors influencing warfarin metabolism, maintenance dosing, and variability. Several dosing models used to predict warfarin dosing (initial or refinement) have been retrospectively evaluated in diverse patient populations. There are several arguments to support incorporating its use in current clinical practice; however, many expert clinicians in anticoagulation have expressed concern that the push for genotyping patients for CYP2C9 ...Continue Reading

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