非瓣膜病心房颤动患者VKORC1及CYP2C9基因多态性与华法林临床应用的关系

Relationship of VKORC1 and CYP2C9 gene polymorphism and warfarin in patients with non-valvular atrial fibrillation

目的:评价VKORC1与CYP2C9基因多态性指导非瓣膜性房颤患者华法林临床应用价值。方法:选择住院治疗非瓣膜性房颤患者290例,记录基线资料,华法林初始剂量和基础国际标准化比率(INR)测定结果,并进行随访;记录初始服用华法林到INR首次达标的时间、华法林总用量和平均每日用量。所有入选者提取静脉血进行目标基因VKORC1与CYP2C9多态性检测。结果:VKORC1 AG/GG基因型患者比AA型患者INR达标时间延长,且INR达标时所需华法林的总量高于AA型患者[(103.38±65.29)g vs.(53.26±24.02)g,P<0.05]。CYP2C9基因型变异患者INR达标时间最短[(9.10±2.01)d vs.(13.07±4.28)d,P<0.05]。且INR达标时所需华法林的总量较少[(28.80±17.35)g vs.(55.45±23.67)g,P<0.05]。结论:非瓣膜性房颤患者初次口服华法林抗凝治疗INR达标时所需华法林剂量个体差异较大,VKORC1 AA基因型患者所需华法林剂量明显低于GG/AG型,CYP2C9基因型AC/CC患者INR达标时间短,达标时所需华法林的剂量较少。

Objective To evaluate the guidance value of VKORC1 and CYP2C9 gene polymorphism on clinical application of warfarin in patients with non-valvular atrial fibrillation（NVAF）. Methods A total of 290 cases of patients with NVAF were identified and their baseline data, initial dose of warfarin and base INR measurement results were recorded, then the follow-up was conducted. The initial administration of warfarin to INR standard time for the first time, total amount of warfarin and the average daily amount were recorded. All participants＇ venous blood was extracted for VKORC1 and CYP2C9 gene polymorphism test. Results VKORC1 AG/GG genotype patients had longer INR standard time and higer amount of warfarin than patients with AA （103.38 ± 65.29）g vs. （53.26 ± 24.02）g, P 〈 0.05. Patients with type CYP2C9 gene mutation had shortest INR standard time（9.10± 2.01）d vs. （13.07 ± 4.28）d, P 〈 0.05. and lowest administration amount of warfarin （28.80 ± 17.35）g vs. （55.45 ±23.67）g, P 〈 0.05. Conclusion There exist significant differences of first adminstration amount of warfarin in patients with NVAF to INR standards. Warfarin dose for VKORC1 AA genotype patients is lower than that for GG/AG type; there is short INR standard time and less adminstration amount of warfarin for CYP2C9 genotypes AC/CC patients.