Interethnic variability of warfarin maintenance requirement is explained by VKORC1 genotype in an Asian population

Abstract

Background: Chinese and Malay subjects have been reported to require less maintenance warfarin than Indians that could not be accounted for by cytochrome P450 (CYP) 2C9 variants. Vitamin K epoxide reductase complex 1 (VKORC1) is the target enzyme of warfarin, and VKORC1 intronic variants and haplotypes have recently been shown to influence VKORC1 activity and warfarin requirements. Methods: We sequenced the coding regions of CYP2C9 and VKORC1 and inferred VKORC1 haplotype from 10 intronic variants in 147 Chinese, 85 Malay, and 43 Indian patients receiving maintenance warfarin. Results: The mean weight-normalized warfarin dose was lower for Chinese and Malays than for Indians (0.058 ± 0.025 mg/kg, 0.059 ± 0.023 mg/kg, and 0.089 ± 0.036 mg/kg, respectively; P < .001 for comparisons between Chinese and Malays with Indians). CYP2C9*2 and VKORC1 coding region variants were rare (