Effect of VKORC1-1639 G>A polymorphism, body weight, age, and serum albumin alterations on warfarin response in Japanese patients.

Introduction: To establish individualized warfarin therapy, we investigated the contribution of genetic variations of vitamin K epoxide reductase complex subunit 1 gene (VKORC1) -1639 G>A and Cytochrome P450 2C9 gene (CYP2C9) and clinical factors on warfarin sensitivity in Japanese patients.

Materials And Methods: Genetic analyses of VKORC1 -1639 G>A and CYP2C9 2, 3, and 4 were performed in 259 Japanese patients and 341 healthy subjects. We selected 259 patients who have been prescribed warfarin with a 1.5-3.0 range of prothrombin time normalized as an international normalized ratio for at least 3 months and investigated factors that contribute to individual variability in warfarin dose. Furthermore, multivariate analysis was performed to investigate a warfarin dosing algorithm.

Results And Conclusions: There were great inter-individual differences in warfarin maintenance dose in 259 patients, ranging from a minimum dose of 0.75 mg/day to a maximal dose of 8.00 mg/day. VKORC1 -1639 G>A polymorphism, body weight, age, and serum albumin were found to affect the inter-individual variability. The dosing algorithm of warfarin maintenance dose was investigated by multivariate linear regression. The regression equation was able to account for 33.2% (R(2)(Adj)=0.332) of the overall variability in warfarin dose.