氯吡格雷基因对急性冠脉综合征患者血小板反应性及主要心血管事件的影响

Effects of clopidogrel associated genes on platelet activity and major cardiovascular events in patients with acute coronary syndrome

目的探讨氯吡格雷基因多态性对急性冠状动脉综合征(ACS)患者血小板反应性及主要心血管事件的影响。方法纳入2019年1-12月在复旦大学附属中山医院行经皮冠状动脉介入(PCI)术的ACS患者149例,所有患者入院后均进行氯吡格雷相关基因型检测。术后规律服用阿司匹林(100 mg/d)和氯吡格雷(75 mg/d)治疗,检测二磷酸腺苷(ADP)诱导的血小板聚集抑制率(IPA)。根据IPA结果,分为氯吡格雷治疗后血小板高反应性(HPR)组(IPA<30%)和氯吡格雷治疗后血小板低反应性(LPR)组(IPA≥30%),分析HPR的相关危险因素及与氯吡格雷基因多态性的关系,同时观察患者随访12个月后主要心血管不良事件(MACE)的发生情况。结果根据IPA结果,HPR组23例(15.44%),LPR组126例(84.56%)。HPR组患者花生四烯酸(AA)诱导的IPA明显低于LPR组,差异有统计学意义(P<0.05)。两组CYP2C19*2、CYP2C19*3、ABCB1和PON1 Q192R功能缺失(LOF)等位基因差异有统计学意义(P<0.05)。多因素logistic回归分析显示,CYP2C19*2 LOF等位基因与PCI术后MACE的发生相关(OR=3.112,95%CI 1.048~9.241,P=0.041)。结论氯吡格雷基因多态性对ACS患者的血小板反应性有一定的影响,CYP2C19*2基因突变与PCI术后MACE的发生有关。

Objective To investigate the effect of clopidogrel genetic polymorphism on platelet reactivity and major cardiovascular events of patients with acute coronary syndrome(ACS).Methods A total of 149 patients with ACS who underwent PCI in Zhongshan Hospital,Fudan University from January to December 2019 were enrolled.All patients were tested for clopidogrel related genotypes after admission.Aspirin(100 mg/d)and clopidogrel(75 mg/d)were taken regularly after operation.The inhibition of platelet aggregation(IPA)induced by adenosine diphosphate(ADP)was detected.According to the results of IPA,patients were divided into two groups:high on-treatment platelet reactivity(HPR)groups(IPA<30%)and low ontreatment platelet reactivity(LPR)groups(IPA≥30%)after clopidogrel treatment.The risk factors of HPR and the relationship between HPR and clopidogrel genetic polymorphism were analyzed.Meanwhile,the incidence of major adverse cardiovascular events(MACE)was observed after 12 months of follow-up.Results According to the results of IPA,there were 23 cases(15.44%)in HPR group and 126 cases(84.56%)in LPR group.Arachidonic acid(AA)induced IPA in HPR group was significantly lower than that in LPR group(P<0.05).The LOF alleles of CYP2C19*2,CYP2C19*3,ABCB1 and PON1 Q192R were significantly different between the two groups(P<0.05).Multivariate logistic regression analysis showed that CYP2C19*2 LOF alleles were associated with MACE after PCI(OR=3.112,95%CI:1.048-9.241,P=0.041).Conclusion Clopidogrel genetic polymorphism has effects on platelet reactivity in patients with ACS.CYP2C19*2 genetic mutation is associated with MACE after PCI.