冠心病介入治疗患者CYP2C19基因多态性与氯吡格雷疗效的相关性研究  

Association between CYP2C19 polymorphisms and clopidogrel pharmacodynamics in patients with coronary heart disease undergoing PCI

作　　者：张晓星[1] 闫丽荣[1] 王冬雪[1] 韩璐璐[1] 李彦[1] 刘红[1] 刘玉清[1] 李一石[1] 

机构地区：[1]中国医学科学院北京协和医学院暨阜外心血管病医院临床药理中心,卫生部心血管药物临床研究重点实验室,北京100037

出　　处：《中国新药杂志》2014年第1期67-71,85,共6页Chinese Journal of New Drugs

基　　金：国家科技部"重大新药创制"科技重大专项(2012ZX09303008-001);国家临床重点专科建设项目(卫生部重点实验室);北京协和医学院研究生创新基金(2012-1002-033)

摘　　要：目的:在服用氯吡格雷的冠心病介入治疗患者中,研究CYP2C19基因多态性及其对围术期血小板聚集率和心肌酶学指标的影响。方法:前瞻性入选非急诊PCI冠心病患者,进行术前CYP2C19基因型、ADP诱导的血小板聚集率,以及心肌酶学指标cTNI的检测,并在所有接受了冠状动脉支架植入治疗的患者中进行术后24 h的cTNI复测。根据患者是否存在CYP2C19功能丧失性等位基因(*2或*3)将其分为非携带组与携带组,比较两组患者在PCI术前的血小板聚集率,以及术前和术后的cTNI之间是否存在差异。结果:在总共入选的365例接受了冠状动脉支架植入的患者中,CYP2C19功能丧失性等位基因非携带组150例(41.1%),携带组215例(58.9%)。其中携带*2位点等位基因的患者199例(54.5%),包括杂合型161例(44.1%)及纯合型38例(10.4%);携带*3位点等位基因的患者24例(6.6%),均为杂合型。非携带组与携带组间的血小板聚集率存在显著性差异(52.2±13.2)%vs(58.9±11.1)%,P<0.001)。两组患者的cTNI水平在PCI术后均较术前有显著升高,其中非携带组由0.027 ng·mL-1升高至0.409 ng·mL-1(P=0.002),携带组由0.038 ng·mL-1升高至0.318 ng·mL-1(P<0.001),但同一时期内组间cTNI水平无统计学差异(P均>0.05)。结论:携带CYP2C19功能丧失性等位基因可导致氯吡格雷抗血小板作用减弱,但并不影响非急诊PCI患者术后24 h内的cTNI水平。Objective：To investigate whether CYP2C19 polymorphisms account for the differences ol the pharmacodynamics indexes of clopidogrel including platelet function and cardiac enzyme in patients with coronary heart disease undergoing PCI. Methods：Patients with coronary heart disease undergoing PCI were recruited pro- spectively and divided into two groups according to TaqMan assay result whether the patients carried any CYP2C19 ＊ 2/ ＊ 3 loss-of-function （LOF） allele or not. Platelet aggregation induced by ADP before PCI and cTNI before and 24 hours after PCI were measured and compared in patients who received coronary stent implementation be-tween groups. Results：Three hundred and sixty-five patients underwent coronary stent placement, among whom 150 were assigned into non-carrier group and 215 into carrier group. One hundred and ninety-nine patients carried at least one LOF allele of ＊ 2, including 161 heterozygotes and 38 homozygotes, and 24 patients were heterozygotes with only one LOF allele of ＊ 3. The platelet aggregation was significantly lower in the non-carrier group （52.2 _＋ 13.2% ） than carrier group （58.9 ＋ 11. 1 ）%, P 〈 0. 001 ）. cTNI increased significantly after PCI procedure as compared with baseline in both non-carrier group and carrier group [ （0. 409 1. 483 ） vs （0. 027 ＋ 0. 148） ng mL-1, P=0.002; （0.318 ＋0.986） vs （0.038 ＋0.232） ng.mL-1, P〈O. 0011, but did not differ between groups in the same period （P 〉 0.05 ）. Conclusion： CYP2C19 LOF allele carriage may reduce the anti-platelet function of clopi- dogrel, but has no effect on the cTNI level within 24 hours after elective PCI procedure.

关 键 词：氯吡格雷 基因多态性 血小板聚集率 心肌酶 

分 类 号：R972[医药卫生—药品]