title: [Possible application of pharmacogenomics to warfarin therapy].
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan. murata@sc.itc.keio.ac.jp
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D019735:Carbon-Carbon Ligases; D065729:Cytochrome P-450 CYP2C9; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D044469:Racial Groups; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase