氯吡格雷在老年缺血性脑卒中患者的应用及CYP2C19基因多态性对预后的影响

Application of clopidogrel in elderly patients with ischemic stroke and influence of CYP2C19 gene polymorphism in prognosis

目的探讨氯吡格雷在老年缺血性脑卒中患者中的应用及细胞色素P4502C19(CYP2C19)基因多态性对预后的影响。方法选取收治的老年缺血性脑卒中患者144例,依据氯吡格雷抵抗情况将这些患者分为抵抗组(n=45)和非抵抗组(n=99)两组,测定两组患者的血小板聚集功能并检测其基因型,然后对2个单核苷酸多态性(SNPs)的等位基因频率及基因型频率、两组患者的2个SNPs分布情况进行统计分析。结果 CYP2C19(636G>A,rs4986893)(681G>A,rs4244285)等位基因及基因频率均和Hardy-Weinberg相符(P>0.05);抵抗组患者的CYP2C19*2(rs4244285)GG型分布率显著低于非抵抗组(P<0.05),GA+AA型分布率显著高于非抵抗组(P<0.05),且GA+AA型分布率显著高于GG型(P<0.05),但两组患者的CYP2C19*3(rs4986893)GG型、AG+AA型分布率之间均差异无统计学意义(P>0.05)。结论老年缺血性脑卒中患者的氯吡格雷抵抗和CYP2C19*2(rs4244285)GA+AA型关系密切,检测该基因型能够为氯吡格雷的临床科学应用提供有效指导,值得临床充分重视。

a Objective To investigate the application of clopidogrel in elderly patients with ischemic stroke and influence of CYP2C19 gene polymorphism in prognosis. Methods One hundred and forty-four cases of elderly patients with ischemic stroke in department of neurology,Wuhan Third Hospital from May 2014 to May 2016 were selected. These patients were assigned into resistance group（n = 45） and non-resistance group（n = 99）,according to the situation of clopidogrel resistance. The platelet aggregation of the two groups were measured and the genotype were detected. then the 2 SNPs allele frequency distribution,genotype frequency of 2 SNPs of the two groups were statistically analyzed. Results CYP2C19（636G 〉 A,rs4986893）（681G 〉 A,rs4244285） allele and gene frequency were consistent with Hardy-Weinberg（P 〉0. 05）. The CYP2C19？2（rs4244285） GG distribution rate of the resistance group was significantly lower than the non-resistance group（P 〈0. 05）,the GA ＋ AA distribution rate was significantly higher than the non-resistance group（P ＆lt;0. 05）,and the GA ＋ AA distribution rate was significantly higher than the GG（P ＆lt;0. 05）. However,the differences of the CYP2C19？3（rs4986893） GG type and AG ＋ AA type distribution rates between the two groups were not significant（P 〉0. 05）. Conclusions The relationship be-tween clopidogrel resistance and GA ＋ AA（rs4244285） CYP2C19？2 of the elderly patients with ischemic stroke is close,the detection of the genotype can provide an effective guidance for the clinical application of clopidogrel,which is worthy of the clinical full attention.