急性脑梗死患者基因多态性对氯吡格雷疗效及终点事件的影响

目的探讨急性脑梗死患者基因多态性对氯吡格雷疗效及终点事件的影响。方法选取2016-06—2017-06新乡市第一人民医院神经内科收治的急性脑梗死患者418例。口服氯吡格雷5 d后抽取外周肘静脉血,血栓弹力图仪测定血小板抑制率。采用改良多重高温连接酶检测反应技术(iMLDR)对患者CYP2C19与ABCBl基因多态性进行分型。出院后进行24个月的随访,记录主要终点事件发生类别及时间。结果根据CYP2C19*2/*3快速代谢型、中间代谢型、慢代谢型的血小板抑制率之间,以及ABCBl C3435T不同基因型之间差异均有统计学意义(P<0.01);而ABCBlT(-620)C不同基因型的血小板抑制率之间差异无统计学意义(P>0.05)。校正可能的混杂因素后,进行多元线性回归分析显示,CYP2C19*2/*3、ABCBl C3435T是血小板抑制率的独立影响因素;同时还发现体重指数(BMI)>26 kg/m2也是血小板抑制率的独立影响因素。共382例患者完成随访研究,终点事件发生率为13.61%(52/382),其中缺血性脑卒中复发36例(9.42%),心肌梗死4例(1.05%),血管性死亡12例(3.14%)。根据是否携带CYP2C19*2/*3基因分为2组,生存分析Log-Rank检验显示差异有统计意义(P<0.05);而ABCBlT(-620)C、ABCBl C3435T基因的显性与阴性患者生存曲线间差异无统计学意义(P>0.05)。多因素Cox回归分析显示,CYP2C19*2/*3基因携带是临床终点时间的独立危险因素;同时年龄也是临床终点时间的独立危险因素。结论携带CYP2C19*2/*3、ABCBl C3435T等位基因的急性脑梗死患者氯吡格雷疗效降低,其中携带CYP2C19*2/*3等位基因的患者终点事件风险增高。

Gene polymorphism on clopidogrel efficacy and endpoint events in patients with acute cerebral infarction

Objective To investigate the effect of gene polymorphism on the efficacy and end-point events of clopidogrel in patients with acute cerebral infarction.Methods 418 patients with acute cerebral infarction were selected from June 2016 to June 2017.After taking clopidogrel orally for 5 days,peripheral elbow venous blood was drawn and platelet inhibition rate was measured by thromboelastograph.The polymorphisms of CYP2C19 and ABCBl genes were typed by improved multiple hyperthermic ligase detection reaction(iMLDR).A 24-month follow-up was conducted after discharge to record the type and time of major endpoint events.Results According to the platelet inhibition rates of CYP2C19*2/*3 fast metabolic type,intermediate metabolic type,slow metabolic type,and ABCBl C3435T genotypes,there were significant differences(P<0.01),but there was no significant difference between ABCBlT(-620)C genotypes(P>0.05).After adjusting for possible confounding factors,multiple linear regression analysis showed that CYP2C19*2/*3 and ABCBl C3435T were independent influencing factors of platelet inhibition rate,and body mass index(BMI)>26kg/m2 was also an independent influencing factor of platelet inhibition rate.A total of 382 patients completed the follow-up study.The incidence of endpoint events was 13.61%(52/382),including 36 cases of recurrent ischemic stroke(9.42%),4 cases of myocardial infarction(1.05%)and 12 cases of vascular death(3.14%).The CYP2C19*2/*3 gene was divided into two groups according to whether CYP2C19*2/*3 gene was carried or not.Survival analysis log-rank test showed that the difference was statistically significant(P<0.05).There was no significant difference between the dominant and negative survival curves of ABCBlT(-620)C and ABCBl C3435T genes(P>0.05).Multivariate Cox regression analysis showed that CYP2C19*2/*3 gene carrier was an independent risk factor for clinical endpoint time,and age was also an independent risk factor for clinical endpoint time.Conclusion Clopidogrel is less effective in patients with acute cerebral infarction carrying CYP2C19*2/*3 and ABCBl C3435T alleles,and the risk of endpoint events is higher in patients with CYP2C19*2/*3 alleles.