CYP2C9、CYP4F2、GGCX和VKORC1基因多态性对房颤患者华法林使用剂量的影响

目的:探讨CYP2C9、CYP4F2、GGCX和VKORC1基因多态性对房颤患者华法林使用剂量的影响。方法:采用PCR-RFLP法检测157例口服华法林抗凝治疗房颤患者CYP2C9、CYP4F2、GGCX和VKORC1基因多态性,登记并计算患者INR稳定在1.5~3.0时一周的平均日剂量。比较不同基因型房颤患者华法林日用量的差异。结果:INR稳定在1.5~3.0时,CYP2C9*1/*1个体使用华法林剂量(2.73±0.80)mg·d^-1]显著高于*1/*3使用量(1.83±0.51)mg·d^-1];VKORC1TT基因型携带者使用剂量(2.56±0.79)mg·d^-1]显著低于CT基因携带者使用量(3.31±0.75)mg·d^-1];CYP4F2 CC基因型使用剂量(2.58±0.78)mg·d^-1]显著低于TT基因携带者使用量(3.21±1.04)mg·d^-1];GGCX CC基因型使用剂量(2.49±0.89)mg·d^-1]显著低于GG基因型使用量(3.04±0.75)mg·d^-1]。多因素回归分析结果显示CYP2C9、VKORC1和GGCX与个体华法林剂量有关。结论:CYP2C9、VKORC1和GGCX基因多态性可能与个体华法林使用剂量差异有关。

Effects of CYP2C9, CYP4F2, GGCX and VKORC1 polymorphisms on warfarin dose in patients with atrial fibrillation

OBJECTIVE To investigate effects of CYP2C9, CYP4F2, GGCX and VKORC1 gene polymorphisms on warfarin dose in patients with atrial fibrillation. METHODS PCR-RFLP method was used to detect CYP2C9, CYP4F2, GGCX and VKORC1 polymorphisms in 157 patients with atrial fibrillation treated by oral anticoagulant. Meanwhile an average daily warfarin dose (for one week) was collected when INR value was maintained stably at 1.5-3.0. Difference of warfarin dose was compared between different genotypes. RESULTS When INR became stable at 1.5-3.0, warfarin dose of CYP2C9 *1/*1 genotype carriers(2.73±0.80)mg·d^-1] was significantly higher than *1/*3 genotype carriers(1.83±0.51)mg·d^-1]; warfarin dose of VKORC1TT genotype carriers(2.56±0.79)mg·d^-1] was significantly lower than that of CT gene carriers(3.31±0.75)mg·d^-1]; dose of CYP4F2 CC genotype dose(2.58±0.78)mg·d^-1] was significantly lower than TT carriers(3.21±1.04)mg·d^-1]; dose of GGCX CC genotype carriers(2.49±0.89)mg·d^-1] was significantly lower than GG genotype carriers(3.04±0.75)mg·d^-1]. Multivariate regression analysis showed that CYP2C9, VKORC1 and GGCX were associated with individual warfarin doses. CONCLUSION CYP2C9, VKORC1 and GGCX polymorphisms may be associated with individual differences of warfarin doses.