[Possible application of pharmacogenomics to warfarin therapy].

Vitamin K-dependent gamma-carboxylation system is crucial to generate active coagulation factors. It consists of gamma-Glutamylcarboxylase (GGCX) and vitamin K-epoxide reductase (VKOR). Warfarin is an anticoagulant that blocks VKOR. Recent studies have shown that genetic variations in a subunit of VKOR complex, VKORC1, and in cytochrome P 450 (CYP) 2C9 genes are strong determinants of individuals' warfarin sensitivity. Algorithms have been proposed to predict warfarin doses, and about 55% of the variance in warfarin dose could be attributed to variations in the VKORC1 and CYP2C9 genes together with age, sex, body-surface area, and presence or absence of heart valve replacement. Contributions of polymorphisms in VKORC1 and CYP2C9 to inter-individual differences of warfarin dose, however, are different among races. Studies have shown that potential clinical and economic benefits of CYP2C9/VKORC1 genotype-guided dosing are only marginal. Thus, evidence is still limited and application of warfarin pharmacogenomics to clinical practice at present needs careful consideration.