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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PCRRFLP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。
Objective: To investigate the effects of CYP2C9, CYP4F2, GGCX and VKORC1 gene polymorphisms on warfarin dosage in atrial fibrillation patients. Methods: The polymorphisms of CYP2C9, CYP4F2, GGCX and VKORC1 in 157 patients with atrial fibrillation treated with warfarin were detected by PCR-RFLP. The mean daily dose of INR for one week was recorded and calculated. Differences in daily dosage of warfarin between patients with different genotypes of AF were compared. Results: The warfarin dose (2.73 ± 0.80 mg · d -1) in CYP2C9 * 1 / * 1 individuals was significantly higher than that of * 1 / * 3 [1.83 ± 0.51) mg · d -1]. The dose of [2.56 ± 0.79] mg · d -1] of carriers of VKORC1TT genotype was significantly lower than that of carriers of CT gene [(3.31 ± 0.75) (2.58 ± 0.78) mg · d -1] for CYP4F2 CC genotype was significantly lower than that of TT gene carriers [(3.21 ± 1.04) mg · d ~ (-1) (-1)]. The dosage of GGCX CC genotype was significantly lower than that of GG genotype [(3.04 ± 0.75) mg · d -1] (2.49 ± 0.89 mg · d -1) . Multivariate regression analysis showed that CYP2C9, VKORC1 and GGCX were related to individual warfarin dose. Conclusion: The polymorphisms of CYP2C9, VKORC1 and GGCX may be related to the dose difference of individual warfarin.