细胞色素P_(450) 2C19基因多态性与缺血性卒中患者氯吡格雷抗血小板聚集作用的关系  

Relationship between cytochrome P_(450)2C19 gene polymorphism and antiplatelet effect of clopidogre in patients with ischemic stroke

作　　者：罗毅 方琪[2] 张坦 黄晨蓉 符昱 朴泉宇 

机构地区：[1]苏州市中西医结合医院脑病科,215101 [2]苏州大学附属第一医院神经内科

出　　处：《中国脑血管病杂志》2015年第10期515-519,共5页Chinese Journal of Cerebrovascular Diseases

基　　金：苏州市科技发展计划(应用基础研究-医疗卫生)项目(SYS201270)

摘　　要：目的探讨缺血性卒中患者细胞色素P450(CYP)2C19*2、*3位点基因多态性与氯吡格雷抗血小板聚集作用的关系。方法前瞻性收集2012年11月至2014年2月苏州市中西医结合医院新入院的急性缺血性卒中患者102例为研究对象,并排除对氯吡格雷过敏、不能耐受者及近期曾使用氯吡格雷者等。根据CYP2C19*2、*3基因位点突变的情况分为强代谢型组(39例)、中间代谢型组(54例)和弱代谢型组(9例)。采用直接测序法测定所有患者CYP2C19*2、*3位点的基因型,并于服用氯吡格雷75 mg/d前及7 d后检测最大血小板聚集率(MAR)和血小板反应指数(PRI),并进行3组间的比较。结果 (1)按CYP2C19*2和CYP2C19*3进行基因分型,强代谢型组包括*1/*1型39例(38.2%);中间代谢型组包括*1/*2型44例(43.1%),*1/*3型10例(9.8%);弱代谢型组包括*2/*2型7例(6.9%),*2/*3型2例(2.0%);未检测出*3/*3型。(2)3组患者服用氯吡格雷前MAR的差异均无统计学意义(均P>0.05)。服用氯吡格雷7 d后MAR、PRI由强到弱依次为弱代谢型组[分别为(49±12)%、(64±15)%]、中间代谢型组[分别为(42±13)%、(56±14)%]和强代谢型组[分别为(33±10)%、(43±12)%],MAR降低幅度由高到低依次为强代谢型组[(20±12)%]、中间代谢型组[(10±8)%]和弱代谢型组[(7±3)%],中间代谢型组和弱代谢型组与强代谢型组比较,MAR、MAR降低幅度和PRI的差异均有统计学意义(均P<0.01),弱代谢型组与中间代谢型组比较,MAR、MAR降低幅度和PRI的差异均无统计学意义(均P>0.05)。结论 CYP2C19*2、*3位点基因多态性可能影响缺血性卒中患者服用氯吡格雷后的MAR和PRI。Objective To investigate the relationship between cytochrome P450（ CYP） 2C19＊ 2 /＊ 3gene polymorphism and antiplatelet effect of clopidogre in patients with ischemic stroke. Methods A total of 102 consecutive patients with acute ischemic stroke admitted to the Suzhou Integrated Traditional and Western Medicine Hospital from November 2012 to February 2014 were enrolled. The patients allergic to clopidogre,intolerant to clopidogrel,and recently using clopidogre were excluded. The patients were divided into a strong metabolic type group（ n = 39）,a moderate metabolic type group（ n = 54）,and a week metabolic type group（ n = 9） according to the conditions of CYP2 C19 ＊ 2 and ＊ 3 locus mutation. The genotypes of the CYP2C19＊ 2 and ＊ 3 were detected by the direct gene sequencing method in all patients.The maximum aggregation ratio（ MAR） of platelet and platelet reactivity index（ PRI） were detected before and 7 d after taking clopidogre 75 mg. Results（ 1） According to the CYP2C19 ＊ 2 and CYP2C19 ＊ 3,the genotyping was performed. The strong metabolic type group included ＊ 1 / ＊ 1 type 39 cases（ 38. 2%）;the moderate metabolic type group included ＊ l / ＊ 2 type 4 4 cases（ 4 3. 1 %）; ＊ l / ＊ 3 5 4 cases,1 0（ 9. 8 %）; and the week metabolic type group included ＊ 2 / ＊ type 27 cases（ 6. 9%）; ＊ 2 / ＊ 3 type2 cases（ 2. 0%）. No ＊ 3 / ＊ 3 type was detected.（ 2） There were no significant differences in MAR before taking clopidogrel among the 3 groups（ all P〉0. 05）. After taking clopidogrel for 7 days,MAR and PRI were detected from strong to weak,followed by the week metabolic type group（ 49 ± 12% vs. 64 ± 15%）,the moderate metabolic type group（ 42 ± 13% vs. 56 ± 14%）,and the strong metabolic type group（ 33 ±10% vs. 43 ± 12%）; MAR was detected from high to low,followed by the strong metabolic type group（ 20 ± 12%）,the moderate metabolic type group（ 10 ± 8%）,and the week metabolic type group（ 7 ±3%）. Compa

关 键 词：卒中 缺血性卒中 基因 细胞色素P450酶系统 氯吡格雷抵抗 血小板聚集率 

分 类 号：R743.3[医药卫生—神经病学与精神病学]