基因多态性对HVR患者华法林起始抗凝效果的影响

Research on the Influence of VKORC1 and CYP2C9 Polymorphisms with Warfarin Initial Anticoagulant Effect

目的:观察心脏瓣膜置换术后患者基线信息和CYP2C9*3、VKORC1-1639A/G基因多态性与术后华法林初始抗凝效果的关系。方法:收集患者的遗传信息和人口统计学信息,同时记录测得的INR值、华法林剂量、达标天数等。结果:纳入的172例患者中,VKORC1-1639AG型患者达到目标INR的时间与AA型相比约延长79.6%;CYP2C9*1/*3型患者达到目标INR的时间与*1/*1型相比约缩短50.9%:大部分VKORC1-1639AA(77.6%)和CYP2C9*1/*1(68.2%)基因型患者能够在术后第7日达到目标INR值;VKORC1-1639AG突变杂合子患者只有23%术后第7日达到目标INR值,且无抗凝过度现象;CYP2C9*1/*3突变杂合子患者全部达到目标INR值,且较易引起抗凝过度。结论:华法林起始抗凝阶段,VKORC1-1639AG突变型患者更难达到目标INR值,CYP2C9*1/*3突变型患者更易达到目标INR值。患者用药前可进行基因型检测,预测华法林用药剂量。

Objective：To explore the relationship between the baseline information and the reponse of VKORC1 and CYP2C9 polymorphisms of patients after heart valve replacement （HVR） to warfarin during initial anticoagulation. Methods：The patients＇ genetic and demographic information was collected and their INR value, dosage of warfarin and days of obtaining target INR value were recorded. Results ： Of 172 consecutive patients, the mean time to target INR value for the patients with VKORCl-1639AG genotype were 79.6% longer than those with VKORCl-1639AA genotype; the mean time to target INR value for the patients with CYP2C9 ＊ 1/＊ 3 genotype was 50.9% shorter than those with CYP2C9 ＊ 1/ ＊ 1 genotype; most patients with VKORCl-1639AA genotype or CYP2C9 ＊ 1/＊ 1 genotype could reach the target INR val-ue on the seventh day postoperatively. Conclusion： It took longer time for the patients with VKORCl-1639AG genotype to obtain the target INR value and shorter time for patients with CYP2C9 ＊ 1/＊ 3 genotype to obtain the target INR value. Pa-tients should have their genotype detection before taking the medicine to predict the dose of warfarin.