摘要
目的探讨ABCB1、CYP2C19、CES1基因多态性与缺血性脑卒中患者氯吡格雷抵抗的关系及其对临床疗效的影响。方法选取2016年10月至2017年12月期间被诊断为缺血性脑卒中的患者90例,均给予氯吡格雷及阿司匹林双抗治疗。通过流式细胞仪检测血小板聚集率,采用焦磷酸测序法进行ABCB1 C3435T、CYP2C19*2、CYP2C19*3及CES1 A816C基因型检测。根据血小板抑制率把患者分为氯吡格雷反应不全组(血小板抑制率<30%)与反应良好组(血小板抑制率≥30%)。观察患者在服用氯吡格雷治疗后12个月内的主要终点事件和临床转归情况。结果90例患者中,氯吡格雷反应不全38例(42.2%),氯吡格雷反应良好52例(57.8%)。氯吡格雷反应良好与反应不全患者性别、年龄、BMI值、吸烟史、饮酒史、高血压史、糖尿病史、血脂异常史、合并使用质子泵抑制剂(PPI)、心肌梗死等基本情况差异无统计学意义(P>0.05);氯吡格雷反应良好与反应不全组ABCB1 C3435T、CES1 A816C基因型分布差异无统计学意义(P>0.05),CYP2C19*2及CYP2C19*3基因型分布差异具有统计学意义(P<0.001)。随访失访率为14.4%。氯吡格雷治疗后缺血事件13例(16.7%),出血事件4例(5.2%),临床疗效良好(Rankin评分≤2)59例(76.6%)。ABCB1 C3435T、CYP2C19*2和CYP2C19*3野生型与突变型患者比较氯吡格雷治疗后缺血事件、预后良好情况,以及出血事件差异无统计学意义(P>0.05),CES1 A816C野生型与突变型患者比较氯吡格雷治疗后出血事件差异有统计学意义,突变型基因更易发生出血事件(P<0.05)。结论氯吡格雷对缺血性脑卒中疗效较好。氯吡格雷治疗缺血性脑卒中过程中,CYP2C19*2及CYP2C19*3基因型可能对血小板抑制率有影响,CES1 A816C基因可能对临床出血事件有影响。
Objective To explore the relationship between ABCB1,CYP2C19,CES1 gene polymorphisms and clopidogrel resistance in ischemic stroke patients and its effect on clinical efficacy.Methods Patients(90 cases)with ischemic stroke from October 2016 to December 2017 were enrolled.Patients were administered with clopidogrel and aspirin once daily.The inhibitory rates of ADP receptor pathway in platelets were detected by flow cytometry,and the genotype of ABCB1 C3435T,CYP2C19*2,CYP2C19*3 and CES1 A816C were detected by pyrosequencing.Patients were divided into two groups:semi-responders(platelet inhibition rate<30%)and the responders(platelet inhibition rate≥30%).The primary endpoint events and clinical outcomes were observed within 12 months.Results In 90 patients,38(42.2%)were classified as clopidogrel semi-responders,52(57.8%)were classified as clopidogrel responders.The history of smoking,drinking,high blood pressure,diabetes,hypertension,dyslipidemia,combined use of proton pump inhibitors and myocardial infarction were not significantly different between the 2 groups(P>0.05).ABCB1 C3435T and CES1 A816C had no influence on platelet inhibition(P>0.05),while CYP2C19*2 and CYP2C19*3 were associated with platelet inhibition(P<0.001).The follow-up loss rate was 14.4%.After 12 months,treatment with clopidogrel,there were 13 cases(16.7%)with ischemia events,4 cases(5.2%)with hemorrhagic events,or 59 cases(76.6%)with good clinical outcomes(modified Rankin Scale≤2).ABCB1 C3435T,CYP2C19*2 and CYP2C19*3 were not correlated with ischemic events,bleeding events or clinical outcomes(P>0.05).CES1 A816C is related to bleeding events,816C was risk factor for bleeding events(P<0.05).Conclusions Clopidogrel has a good effect in the treatment of ischemic stroke.In the treatment of ischemic stroke,CYP2C19*2 and CYP2C19*3 are related to platelet inhibition,CES1 A816C is related to clinical bleeding events.
作者
刘亚巍
赵小朗
姚璞
程林
孙凤军
曹秋婷
LIU Yawei;ZHAO Xiaolang;YAO Pu;CHENG Lin;SUN Fengjun;CAO Qiuting(不详;Department of Pharmacy,the First Affiliated Hospital of Army Medical University,Chongqing 400038,China)
出处
《中国神经免疫学和神经病学杂志》
CAS
北大核心
2021年第2期146-151,共6页
Chinese Journal of Neuroimmunology and Neurology
基金
重庆市社会事业与民生保障科技创新专项分课题(cstc2016shma-ztcs10004)。
