CYP2C19基因多态性与氯吡格雷治疗缺血性脑卒中复发风险的相关性研究Association of CYP2C19 gene polymorphism with the relapse risk of ischemic stroke treated by clopidogrel
张建平,李志强,贺显君,代允义,路文革,徐忠海
ZHANG Jian-ping,LI Zhi-qiang,HE Xian-jun,DAI Yun-yi,LU Wen-ge,XU Zhong-hai
摘要(Abstract):
目的探讨CYP2C19基因多态性与氯吡格雷治疗缺血性脑卒中复发风险的相关性。方法规律服用氯吡格雷常规治疗剂量≥1a的缺血性脑卒中患者147例,根据有无卒中复发分为无卒中复发组119例和卒中复发组28例,2组应用PCR限制性片段长度多态性方法检测CYP2C19*2、*3基因型,采用多因素logistic回归分析其对缺血性脑卒中复发的影响。结果卒中复发组患者合并糖尿病(39.3%)、既往卒中史比率(28.6%)高于无卒中复发组(19.3%、11.8%)(P<0.05);卒中复发组CYP2C19*1/*1基因型和*1等位基因频率(28.6%、53.6%)低于无卒中复发组(46.2%、67.2%)(P<0.05),CYP2C19*2/*2基因型和*2等位基因频率(14.3%、39.3%)高于无卒中复发组(6.7%、26.9%)(P<0.05);卒中复发组CYP2C19*3等位基因频率(7.1%)与无卒中复发组(5.9%)比较差异无统计学意义(P>0.05);多因素logistic回归分析显示,糖尿病(OR=4.215,95%CI:1.284~12.214,P=0.008)、既往卒中史(OR=3.236,95%CI:1.324~10.329,P=0.015)和CYP2C19*2等位基因(OR=2.792,95%CI:1.245~6.436,P=0.014)是卒中复发的独立危险因素。结论携带CYP2C19*2等位基因的缺血性脑卒中患者氯吡格雷治疗效果差,卒中复发的风险增高。
Objective To investigate the association between CYP2 C19 gene polymorphism and the relapse risk of ischemic stroke treated by clopidogrel.Methods A total of 147 patients with ischemic stroke receiving regularly oral administration of clopidogrel in conventional dose for 1 year or more were divided into relapse group(n=119)and no-relapse group(n=28).PCR-restriction fragment length polymorphism was used to detect CYP2 C19 *2 and *3 genotype,and multivariate logistic regression analysis method was used to study their influences on the relapse of ischemic stroke.Results The rates of complicated diabetes and stroke history were significantly higher in relapse group(39.3%,28.6%)than those in no-relapse group(19.3%,11.8%)(P<0.05).The frequencies of CYP2 C19 *1/*1 genotype and *1 allele were significantly lower in relapse group(28.6%,53.6%)than those in no-relapse group(46.2%,67.2%)(P<0.05),while the frequencies of CYP2 C19 *2/*2 genotype and *2 allele were significantly higher in relapse group(14.3%,39.3%)than those in no-relapse group(6.7%,26.9%)(P<0.05).There was no significant difference in the frequency of CYP2 C19 *3 allele between relapse group(7.1%)and no-relapse group(5.9%)(P>0.05).Multivariate logistic regression analysis showed that diabetes(OR=4.215,95%CI:1.284-12.214,P=0.008),stroke history(OR=3.236,95%CI:1.324-10.329,P=0.015),and CYP2 C19 *2 allele(OR=2.792,95%CI:1.245-6.436,P=0.014)were the independent risk factors for stroke relapse.Conclusion In patients with ischemic stroke carrying CYP2 C19 *2 allele,the effect of clopidogrel is poor and the risk for stroke relapse increases.
关键词(KeyWords):
缺血性脑卒中;CYP2C19;基因多态性;氯吡格雷
Ischemic stroke;CYP2C19;gene polymorphism;clopidogrel
基金项目(Foundation): 河南省科技攻关计划项目(152102310029)
作者(Author):
张建平,李志强,贺显君,代允义,路文革,徐忠海
ZHANG Jian-ping,LI Zhi-qiang,HE Xian-jun,DAI Yun-yi,LU Wen-ge,XU Zhong-hai
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