PCI术后高血小板反应与CYP2C19基因多态性关系的分析

目的 观察经皮冠状动脉介入（PCI）术后使用氯吡格雷6个月后其高血小板反应发生率及其与CYP2C 19基因多态性的关系.方法 入选2012年6月至9月行PCI治疗的冠心病患者47例,术前顿服氯吡格雷300mg、阿司匹林300mg负荷剂量,术后予维持剂量治疗.检测术后6个月最大血小板聚集率（MPA）,直接测序法检测CYP2C 19基因多态性.将观察对象分为血小板高反应性（HPR）组和非血小板高反应性（nHPR）组,检测血细胞计数、纤维蛋白原、超敏CRP等及CYP2C 19基因多态性与HPR的关系.结果 HPR17例,nHPR 30例.CYP2C19基因表型强代谢者21例,一般代谢者18例,弱代谢者8例.HPR组,EMs6例（35.3％）,IMs6例（35.3％）,PMs5例（29.4％）;nHPR组,EMs15例（50.0％）,IMs12例（40.0％）,PMs3例（10.0％）.HPR、nHPR组2μmol/L、5μmol/L ADP诱导MPA比较差异有统计学意义（p＜0.01）.EMs、IMs、PMs组间MPA、HPR比较有增高趋势,但差异无统计学意义（P＞0.05）.结论 PCI术后患者中接受氯吡格雷治疗的HPR普遍存在.CYP2C19基因检测相关代谢型与HPR无明确相关性.

Objective We aimed to investigate the relationship between cytochrome （ CYP ） 2C19 ＊2, ＊3 polymorphisms and high ontreatment platelet reactivity （ HPR ） in patients treated with percutaneous coronary interventions （ PCI ） and dual antiplatelet therapy over a 6-month period. Methods Totally 47 patients post-PCI were enrolled from June 2012 to September 2012. Patients received a 300mg loading dose （ LD ） clopidogrel and aspirin before PCI, then continued with maintenance dose （ MD ） as dual antiplatelet therapy. Max platelet aggregation （ MPA ） was assessed in post-PCI patients after 6 months. Direct sequence was used to genotype the CYP2C19＊2, CYP2C19＊3 polymorphisms in these patients. HPR was defined as MPA〉46%, whereas those having〈46% were nHPR. According to CYP2C19 polymorphism, we examined MPA and HPR in different phenotype. Results HPR was present in 36.2% patients. The phenotype of CYP2C19 includes EMs 44.7% （ n=21 ） , IMs 38.3% （ n=18 ） and PMs 17.0% （ n=8 ） . In HPR group and nHPR group, there were EMs 35.3% （ n=6 ） , 50.0% （ n=15 ） , IMs 35.3% （ n=6 ） , 40.0% （ n=12 ） , PMs 29.4% （ n=5 ） , 10.0% （ n=3 ） , respectively. There＇ s no statistic differences among EMs, IMs, PMs in MPA and HPR distribution.Conclusion HPR is common in patients received clopidogrel after PCI. There is no substantial interaetion between CYP2C 19 polymorphism and platelet reactivity on clopidogrel.