血小板膜受体P2Y12基因多态性(C34T和G52T)与冠心病患者介入术后服用氯吡格雷临床预后的相关性研究

目的 探讨血小板膜受体P2Y12 基因多态性(C34T 和G52T)对冠心病患者经皮冠状动脉介入治疗(PCI)术后服用氯吡格雷临床预后的影响.方法 入选2008 年11 月至2009 年11 月收住我院拟行PCI 的冠心病患者268 例,正规服用氯吡格雷12 个月.采用MassARRAY 时间飞行质谱及TaqMan Assay 检测入选患者血小板受体P2Y12 基因C34T 和G52T 两个位点,按基因型对患者进行分组,观察术后1 年间死亡,非致死性心肌梗死、急诊血运重建、支架内血栓形成和心绞痛复发等严重不良心血管事件的发生情况.结果 入选病例按G52T 位点基因型分为H1/H1 型(n ＝195)和H2 携带者(H1/H2 和H2/H2,n ＝73)两组,H1/H1 组双支病变比例高于H2 携带者组(P ＜0.05),两组患者其余临床基本资料均一致,无显著性差异(P ＞0.05).PCI 术后1 年随访期间,两组患者死亡、非致死性心肌梗死、急诊血运重建术等联合终点事件发生率,H2 携带者明显高于H1/H1 组,差异有统计学意义(12.3% vs.5.1%,P ＜0.05).一年累计生存率H2 携带者要低于H1/H1 组(HR ＝2.543,95% CI:1.033 ～6.259,P ＝0.042).两组患者急性心肌梗死、支架内血栓形成、急诊血运重建术和死亡的发生率没有明显统计学差异(P ＞0.05),但H2 携带者心绞痛复发率高于H1/H1 组,有统计学差异(P ＜0.05).入选病例按C34T 位点基因型分为CC 型(n ＝174)和CT/TT 型(n ＝94)两组,两组患者的临床基本资料均匹配(P ＞0.05).PCI 术后1 年随访期间,两组患者联合终点事件发生率和一年累计生存率均无统计学差异(P ＞0.05).结论 血小板膜受体P2Y12 基因H2 携带者可能是中国冠心病患者介入治疗后服用氯吡格雷临床预后的主要影响因素之一,而C34T 位点多态性和介入治疗后服用氯吡格雷临床预后无明显相关性.

Association between P2Y12 platelet receptor(C34T and G52T) polymorphisms and risk of cardiovascular events in coronary heart disease with clopidogrel in Chinese

Objective Recent data have implicated a haplotype of P2Y12 platelet receptor,as potential risk determinant for atherothrombosis.We wanted to investigate whether the platelet P2Y12 receptor polymorphims affected long-term prognosis of Chinese patients who were treated with clopidogrel after percutaneous coronary intervention（PCI） .Methods Between January 1,2008 and December 31,2009,268 patients who received PCI and were exposed to clopidogrel treatment for almost 12 months,were enrolled in Fu Wai Hospital and underwent P2Y12（G52T and C34T） determination.Follow-up was 12 months.The primary endpoint was a composite of death,myocardial infarction,urgent coronary revascularization and stent thrombosis occurring during exposure to clopidogrel.Results The patients were grouped H1 /H1（n = 195） and H2 carriers（H1 /H2 and H2 /H2,n = 73） by P2Y12 G52T genetype.Baseline characteristics were balanced between the two groups,except the proportion of H1 /H1 is higher than H2 carriers in two vessel lesions （P 〈 0.05） .The combined end points also occurred more frequently in H2 carriers than in H1 /H1（12.3% vs.5.1% ,P 〈 0.05 ） .There were no significant difference between two groups with myocardial infarction,stent thrombosis,urgent coronary revascularization and death （P 〉 0.05） .During the following time,cumulative survival of H2 carriers was lower than H1（HR = 2.543,95% CI： 1.033 ～ 6.259,P = 0.042） .The patients were also grouped CC genotype（n = 174） and T carriers（CT and TT,n = 94） by P2Y12 C34T genetype.Baseline characteristics were balanced between the two groups.There were no significant difference between two groups with the combined end points and cumulative survival（HR = 1.081,95% CI： 0.426 ～ 2.746,P = 0.870） .Conclusions P2Y12 platelet receptor H2 haplotype（G52T） is a major determinant of prognosis in Chinese patients with cardiac heart disease（CHD） who are receiving clopidogrel treatment after PCI.But there is not a strong association between C34T and an increased risk of cardiovascular events in patients with CHD receiving clopidogrel.