药物代谢相关基因多态性对急性冠状动脉综合征患者氯吡格雷疗效的影响  

Effect of drug metabolism related gene polymorphism on efficacy of clopidogrel in patients with acute coronary syndrome

作　　者：李洋 霍记平[2] 崔健 王凯 任爽 杨莉[2] Li Yang;Huo Jiping;Cui Jian;Wang Kai;Ren Shuang;Yang Li(Department of Pharmacy,People′s Hospital of Daxing District,Beijing 102600,China;Department of Pharmacy,Beijing Tiantan Hospital,Capital Medical University,Beijing 100071,China)

机构地区：[1]北京市大兴区人民医院药剂科,北京102600 [2]首都医科大学附属北京天坛医院药学部,北京100071

出　　处：《药物不良反应杂志》2022年第10期522-527,共6页Adverse Drug Reactions Journal

基　　金：“十三五”国家重点研发计划(2020YFC2008305)。

摘　　要：目的探讨药物代谢相关基因多态性对急性冠状动脉综合征(ACS)患者氯吡格雷疗效的影响。方法收集2017年至2019年在北京市大兴区人民医院住院、接受阿司匹林(100 mg/d)及氯吡格雷(75 mg/d)标准化治疗且进行了氯吡格雷吸收/代谢相关基因多态性检测的ACS患者病历资料和随访记录,根据患者治疗1年内是否出现心肌梗死、支架内血栓形成、脑梗死等血栓相关事件将患者分为血栓事件组及非血栓事件组,对比2组患者年龄、性别、烟酒嗜好、基础疾病、并用药物及氯吡格雷吸收/代谢相关等位基因等因素;采用logistic回归模型对影响氯吡格雷临床疗效的因素进行分析。结果共有342例患者纳入分析,男性274例,女性68例,年龄(58±9)岁,78例(22.8%)发生血栓事件。血栓事件组与非血栓事件组患者的年龄、性别、吸烟史、饮酒史、高血压病、糖尿病、高脂血症、经皮冠状动脉介入治疗史、并用钙离子通道拮抗剂占比、细胞色素P450(CYP)2C19*3、对氧磷酶‑1基因Q192R及三磷酸腺苷结合盒转运蛋白B1基因C3435T均无明显差异(均P>0.05),但血栓事件组患者体重指数(BMI)、CYP2C19*2 GG型及CYP2C19*17 CT型患者的比例低于非血栓事件组(均P<0.05),并用质子泵抑制剂患者和CYP2C19*17 CC型患者的比例高于非血栓事件组(均P<0.05)。多因素logistic回归分析结果显示,高BMI(OR=0.915,95%CI:0.847~0.989,P=0.026)、CYP2C19*2 GG型(OR=0,95%CI:0~0.008,P<0.001)及GA型(OR=0.028,95%CI:0.003~0.296,P=0.003)是氯吡格雷治疗后发生血栓事件的独立保护因素;CYP2C19*17 CC型(OR=2856.665,95%CI:87.337~93436.810,P<0.001)是氯吡格雷治疗后发生血栓事件的独立危险因素。结论CYP2C19*2和CYP2C19*17突变是ACS患者氯吡格雷疗效和治疗后血栓事件发生的重要影响因素。Objective To investigate the effect of drug metabolism related gene polymorphism on the efficacy of clopidogrel in patients with acute coronary syndrome(ACS).Methods The medical records and follow‑up records of ACS patients,who were hospitalized in the People′s Hospital of Daxing District between 2017 and 2019,received standardized treatment with aspirin(100 mg/day)+clopidogrel(75 mg/day),and underwent testing for genetic polymorphisms related to clopidogrel absorption/metabolism,were collected.The patients were divided into thrombotic event group and non‑thrombotic event group according to whether they experienced thrombotic events such as myocardial infarction,stent thrombosis,and cerebral infarction within 1 year of treatment.The age,gender,smoking history and drinking habits,underlying diseases,drug combination,and alleles related to clopidogrel absorption/metabolism in patients in the 2 groups were compared.The factors affecting the clinical efficacy of clopidogrel was analyzed using logistic regression model.Results A total of 342 patients were included in the analysis,including 274 males and 68 females,aged(58±9)years;of them,78(22.8%)developed thrombotic events.The differences in age,gender,smoking history,drinking history,hypertension,diabetes mellitus,hyperlipidemia,percutaneous coronary intervention history,proportion of combined with calcium channel antagonists,cytochrome P450(CYP)2C19*3,paraoxonase‑1 Q192R,and adenosine triphosphate binding cassette transporter B1 C3435T between the thrombotic event group and the non‑thrombotic event group were not statistically significant(all P>0.05),but the body mass index(BMI),the proportion of CYP2C19*2 GG type and CYP2C19*17 CT type in patients in the thrombotic event group were lower than those in the non‑thrombotic event group(all P<0.05),and the proportion of patients with proton pump inhibitor and CYP2C19*17 CC type in the throm‑botic event group was higher than that in the non‑thrombotic event group(all P<0.05).Multivariate logistic regres

关 键 词：急性冠状动脉综合征 细胞色素P450酶系统 多态性 基因 氯吡格雷 

分 类 号：R541.4[医药卫生—心血管疾病]