CYP2C19基因多态性与冠心病氯吡格雷疗效的关系

Relationship between CYP2C19 gene polymorphism and clinical efficacy of clopidogrel in patients with coronary heart disease

目的:观察CYP2C19基因多态性与新疆汉族人群中冠心病患者氯吡格雷常规剂量抗血小板治疗疗效的关系。方法:选择诊断明确且进行了CYP2C19基因多态性检测的冠心病患者168例,其中包括经PCI术后组99例和经选择性冠状动脉造影术明确诊断多支病变不宜行PCI而又未接受CABG患者69例。根据CYP2C19基因型不同,PCI组又分为快代谢型49例和中慢代谢型50例;多支病变组分为快代谢型34例和中慢代谢型35例;均接受口服常规剂量氯吡格雷75 mg/d加阿司匹林100 mg/d行抗凝治疗1年。对比分析4组院外用药情况、不良心血管事件、出血事件的发生情况。结果:(1)多支病变组β受体阻滞剂和尼可地尔的使用率高于PCI组;PCI组的中慢代谢型和多支病变组硝酸酯类使用率高于PCI组的快代谢型;多支病变组中慢代谢型ACEI/ARB的使用率高于PCI组中慢代谢型和多支病变组的快代谢型(均P<0.05)。(2)多支病变组非致死性心肌梗死发生率高于PCI组(P<0.05);PCI组的中慢代谢型和多支病变组心绞痛的再发率高于PCI组的快代谢型(均P<0.05);而心源性死亡、支架内血栓形成、再次血运重建的发生率4组比较无显著性差异。(3)4组间出血事件发生率均无显著性差异。(4)多因素Logistic回归分析结果显示,CYP2C19*2的基因型、糖尿病病史、高血压病史是发生不良心血管事件的相关因素。结论:CYP2C19基因多态性与PCI后及多支病变冠心病患者院外再发心绞痛、非致死性心肌梗死和口服药物种类有关,CYP2C19*2是不良心血管事件发生的高危因素之一,CYP2C19功能缺失基因的多态性影响抗凝治疗后冠心病患者的预后。

Objective： To investigate the relationship between CYP2C19 gene polymorphism and clinical efficacy of clopidogrel in patients with coronary artery disease （CAD） in Xinjiang. Methods： A total of 168 CAD patients receiving CYP2C19 gene polymorphism detection were enrolled including 99 patients after PCI and 69 patients with multivessel disease diagnosed by selective coronary angiography （ SCA） that were not suitable for PCI and didnh receive coronary artery bypassgrafting# CABG）. According to the different genotype of CYP2C19,PCI group was divided into fast metabolism type（49 cases）and medium-slow metabolism type#50 cases） ’ and multivessel disease group was divided into fast metabolism type（ 34 cases） and medium-slow metabolism type（ 35 cases）. All patients took clopidogrel 75 mg/d and asjDirin 100 mg/d for 1 year. The out- of-hospital drug use , adverse cardiovascular events and bleeding events were compared among the four groups. use of ＂-blockers and nicorandil in multivessel disease group was higher than that in PCI medium-slow metabolism type of PCI group and multivessel disease group was higher tlian that in the fast group. The use of ACEI/ARB was significantly higher in the medium-slow metabolism type of multivvssel diseasin the medium-slow metabolism type of PCI and the fast metabolism type of muincidence of non-fatal myocardial infarction in multivessel disease group was higher tlian those in the recurrent angina pectoris in the medium-slow metabolism type of PCI group and multivessel the fast metabolism type of PCI group （ all P 〈 0. 05 ） . The incidences of cardiac death,stent thrombosis and vascularreconstruction were not significantly different among the four groups. （ 3 ） There was no significant differebleeding events among the four groups. （4） Multivariate Logistic Regression showed that CYP2C19 genotype,hyper and diabetes history were risk factors of adverse cardiovascular events. Conclusion： CYwith recurrent angina,non-fatal myocardial infarction and oral drug types in CAD patients after PCI or witli multivessel disease.CYP2C19 ＂ 2 is one of the high risk factors of adverse cardiovascular events. The CYP2C19 loss-of-function gene polymorphismcould influence CAD prognosis.