CYP2C19基因多态性与氯吡格雷药效的相关性研究

Correlation between CYP2C19gene polymorphism and the efficacy of clopidogrel

目的:探讨服用氯吡格雷的急性冠脉综合征介入治疗患者CYP2C19基因多态性及其与氯吡格雷药效的关系。方法:选择我院急性冠脉综合征并接受经皮冠状动脉介入治疗术(PCI)的患者,采集静脉血提取基因组DNA,根据患者是否存在CYP2C19功能丧失性等位基因(*2或*3)将其分为非携带组与携带组,比较两组PCI术后6个月服用氯吡格雷后主要心血管不良事件(心源性死亡、心肌梗死、支架内血栓形成、脑卒中)发生率是否存在差异。结果:418例PCI患者中,CYP2C19功能丧失性等位基因非携带组180例(43.1%),携带组238例(56.9%),其中172例(41.2%)为野生型基因与突变基因杂合子组(CYP2C19*1/*2和CYP2C19*1/*3),66例(15.7%)为突变基因纯合子或杂合子组(CYP2C19*2/*2、CYP2C19*3/*3和CYP2C19*2/*3)。两组PCI术后6个月主要心血管不良事件发生率分别为8.3%和14.2%,差异有统计学意义(P<0.01)。结论:携带CYP2C19功能丧失性等位基因可导致氯吡格雷抗血小板作用减弱,增加急性冠脉综合征患者PCI术后6个月的主要心血管不良事件发生率。

Objective:To explore the correlation between CYP2C19 gene polymorphism and the efficacy of clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary artery interventional therapy(PCI).Methods:The genomic DNAs were extracted from the peripheral blood samples of 418 patients with acute coronary syndromes undergoing PCI.Patients were divided into two groups according to whether the patients carried nonfunctional CYP2C19allele(*2/*3)or not.The incidence rates of major adverse cardiac events(MACE)including cardiovascular death,myocardial infarction,stent thrombosis and stroke were compared between the two groups after the treatment with clopidogrel for 6 months.Results:All together 238cases(56.9%)were carriers of nonfunctional CYP2C19 allele and others(43.1%)were not among 418 patients,172cases(41.2%)carried the allele of wild-type and mutation-type heterozygote(CYP2C19*1/*2and CYP2C19*1/*3)while 66cases(15.7%)carried the allele of mutant-type homozygote or heterozygote(CYP2C19*2/*2,CYP2C19*3/*3and CYP2C19*2/*3).The incidence rate of MACE was significantly lower in non-carrier group(8.3%)than that in carrier group(14.2%)(P<0.01).Conclusion:Nonfunctional CYP2C19 allele may reduce the anti-platelet function of clopidogrel,and increase the incidence rates of MACE after the treatment with clopidogrel for 6months in patients with acute coronary syndrome undergoing PCI.