Effect of genetic factors on the interindividual variability of warfarin dosage requirements in Japanese patients after adjusting for renal function.

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in <i>VKORC1</i>, <i>CYP2C9</i>, <i>CYP2C19</i>, <i>CYP4F2</i>, <i>GGCX</i>, and <i>APOE</i> in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [<i>VKORC1</i> rs9923231, <i>CYP2C9</i> rs1057910, <i>CYP4F2</i> rs2108622, <i>CYP2C19</i>^* <i>2</i> (rs4244285) and^* <i>3</i> (rs4986893), <i>GGCX</i> rs699664 and rs12714145, and <i>APOE</i> rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (^β = -0.445). <i>VKORC1</i> rs9923231 AA, <i>CYP4F2</i> rs2108622 CT/TT, <i>GGCX</i> rs12714145 CT/TT, and <i>CYP2C9</i> rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and β = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of <i>VKORC1</i> rs9923231, <i>CYP4F2</i> rs2108622, <i>GGCX</i> rs12714145, and <i>CYP2C9</i> rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.