Genes affecting warfarin response-interactive or additive?
Genotypes for cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase complex 1 (VKORC1) contribute significantly to the inter-patient variability in warfarin dose requirements. These genotypes in addition to clinical factors explain approximately 50% of the dose variability in Europeans, but less in other populations. Thus, a large portion of the variability remains unexplained and has been the focus of on-going research. Trials evaluating the clinical utility of genotype-guided warfarin dosing have shown a benefit in Europeans, but not in an ethnically diverse cohort. Identifying and accounting for variants important in non-European populations will likely be necessary before a benefit with genotype-guided dosing will be realized in these populations.
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida at Gainesville, Gainesville, FL, USA.
Larisa H
LH
Cavallari
Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
Julio D
JD
Duarte
D000925:Anticoagulants / Q000008:administration & dosage; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D064417:Vitamin K Epoxide Reductases
CYP2C9; VKORC1; genotype; warfarin