Contribution of 1173C > T polymorphism in the VKORC1 gene to warfarin dose requirements in Han Chinese patients receiving anticoagulation

OBJECTIVE: The objective was to assess 1173C > T polymorphism of the VKORC1 gene and its contribution to warfarin dose requirements in Han Chinese patients. METHODS: Blood samples were collected from 178 patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the target range (1.5 - 3.0). Polymorphisms for VKORC1 (1173C > T), CYP2C9, venous INR, and plasma concentration and unbound concentration of warfarin were analyzed. RESULTS: VKORC1 (1173C > T) genotyping showed that 154 patients were homozygous TT, 23 were heterozygous CT, and one was homozygous for the CC genotype. Patients with the VKORC1 (1173CC + CT) genotype required a significantly higher warfarin dose (3.33 ± 1.04 mg/day) than those with 1173TT (1.81 ± 0.63 mg/day; p < 0.001). The multiple linear regression model for warfarin dose indicated significant contributions from the VKORC1 (1173C > T) genotype (r2 = 0.355; p < 0.001), and age, body weight, and CYP2C9 and VKORC1 genotype together (r2 = 0.513; p < 0.001). The two SNPs (-1639 and 1173) were found to be in very strong linkage disequilibrium with estimated D' = 0.96 (95%CI (0.83 - 0.99)). CONCLUSION: The VKORC1 (1173C > T) polymorphism might be very important, and its contribution can be equally explained by the VKORC1(-1639 G > A) polymorphism for warfarin dose requirements in Han Chinese patients.