细胞色素P450酶2C19基因多态性与缺血性脑血管病患者介入术后服用氯吡格雷临床预后的相关分析  

Relationship between cytochrome P450 2C19 polymorphisms and clinical outcomes in clopidogrel- treated patients who underwent cerebrovascular stenting placement

作　　者：孙文珊[1] 李永坤[1] 张治中[1] 李明泉[1] 王筱萌[1] 田利丽[1] 殷勤[1] 樊小兵[1] 徐格林[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)神经内科,210002

出　　处：《中华神经科杂志》2013年第4期220-223,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目（81070922）;江苏省自然科学基金资助项目（BK2011021）

摘　　要：目的探讨细胞色素P450酶2C19（CYP2C19）基因多态性与缺血性脑血管病患者介入术后长期服用氯吡格雷临床预后的相关性。方法入选南京卒中注册系统中2009年4月至2010年12月行脑血管支架植入术并长期服用氯吡格雷的缺血性卒中患者194例。采用多重高温连接酶检测反应技术对入选病例的CYP2C19＊2和CYP2C19＊3位点进行分型，并对这些患者进行随访。主要终点事件包括缺血性脑血管事件和死亡；次要终点事件包括出血性血管事件和其他血管事件。结果平均随访（19．4±9．9）个月，主要终点事件发生率为16．5％（32／194）。CYP2C19。2基因位点分型结果显示，194例患者中，CYP2C19＊1。1型患者87例（44．8％），CYP2C19＊1＊2型患者88例（45．4％），CYP2C19＊2＊2型患者19例（9．8％）。携带CYP2C19＊2基因的患者随访期间主要终点事件的发生率明显高于非携带者[24／107（22．4％）与8／87（9．2％），HR=2．74，95％CI1．23—6．10，P=0．01]。CYP2C19＊3基因位点分型结果显示，CYP2C19＊1＊1基因型患者181例（93．3％），CYP2C19＊1＊3基因型患者13例（6．7％）。CYP2C19＊1＊1和CYP2C19＊1＊3的两组患者之间主要终点事件发生率的差异无统计学意义。将年龄、性别、体重指数、高血压、糖尿病等危险因素纳入多因素COX回归模型分析显示，CYP2C19＊2是主要终点事件的发生独立危险因素（HR=2．89，95％CI 1．10～7．60，P=0．03）。结论CYP2C19＊2基因位点的多态性可能是影响脑血管支架术后服用氯吡格雷的患者临床预后的重要影响因素。Objective To evaluate the impact of cytochrome P450 （CYP） 2C19 gene polymorphisms on clinical outcome in clopidogrel-treated patients who underwent cerebrovascular stenting placement. Methods One hundred and ninty-four patients who underwent eerebrovascular stent placement and with long-term treatment of elopidogrel （75 mg/d） between April 2009 and December 2010 were enrolled, CYP2CI9 genotype was detected by improved multiple ligase detection reaction. The primary clinical endpoints were isehemic stroke and death after stent implantation; the key secondary endpoints were hemorrhagic stroke and other vascular events. Results The average followed-up was （ 19. 4 ± 9. 9） months. The overall incidence of primary endpoints was 16. 5%. Of the 194 patients,87 （44. 8% ） were wild-type homozygous ,88 （45.4%） were heterozygotes,and 19 （9. 8% ） were homozygous. The cumulative incidence of adverse outcomes was significant higher in CYP2C19 ＊ 2 carrier than that in noncarriers （22. 4% （24/107） vs 9.2% （8/87）, HR = 2. 74, 95% CI 1.23-6. 10, P = 0. O1 ）. Of the 194 patients, 13 （6.7%） were heterozygotes, and 181 （93.3%） were wild-type homozygous. CYP2C19 ＊3 polymorphism had no significant impact on the outcomes in this cohort of patients. No relationship between gene and the secondary endpoints were detected. After multivariable analysis, the CYP2C19＊ 2 was an independent predictor of clinical outcomes of eerebrovaseular stent placement （HR ---2. 89, 95% CI 1.10--7.60, P =0. 03）. Conclusions CYP2C19 ＊ 2 is an independent determinant of adverse events after cerebrovascular stent placement treated with elopidogrel. While CYP2C19＊ 3 is not associated with the clinieal prognosis in patients with eerebrovaseular stent placement.

关 键 词：脑缺血 卒中 芳基烃羟化酶类 多态现象 遗传 支架 噻氯匹定 预后 

分 类 号：R743[医药卫生—神经病学与精神病学]