细胞色素P4503A4+894C>T基因多态性与急性冠脉综合症患者冠状动脉介入术预后的关系

Correlation between cytochrome 3A4+894C>T P450 gene polymorphism and outcomes of coronary intervention in patients with acute coronary syndrome

目的探讨急性冠脉综合征(ACS)患者血浆细胞色素P450 3A4(CYP3A4)894C>T基因多态性与接受经皮冠状动脉介入(PCI)治疗后患者心脏不良事件再发风险的关系。方法入选275例接受标准双联抗血小板及PCI术治疗的ACS患者。在服用抗血小板药物前及7 d后检测每位患者的血小板聚集率(PAR)。采用基因芯片及PCR技术检测每组内患者CYP3A4基因894C>T单核苷酸多态性的基因型和等位基因分布。通过PCI术明确患者的冠脉病变数目并计算其Gensini评分。出院后随访3~12月。结果 CYP3A4基因多态性在氯吡格雷抵抗(CR)组和非氯吡格雷抵抗(NCR)组的差异无统计学意义(P>0.05)。多因素Logistic回归分析显示,CYP3A4基因894C>T位点中携带T突变基因与ACS患者发生CR的相关性差异无统计学意义(OR1.359,P>0.05)。随访3~12月后,CR组较NCR组均有更高的心血管事件发生率(P<0.05),但与CYP3A4基因894C>T位点的突变类型无关。结论 CYP3A4基因894C>T位点的多态性对ACS患者PCI术后抗血小板效应及心血管发生风险无明确指导意义。

Objective To investigate the relationship between plasma cytochrome P450 3A4 （CYP3A4） 894C〉T gene polymorphism and the risk of recurrence of adverse cardiac events after percutaneous coronary intervention （PCI） in patients with acute coronary syndrome （ACS）. Methods A total of 275 patients with ACS received standard dual antiplatelet therapy and PCI. Platelet aggregation rate （PAR） was detected in each patient before and 7 days after administration of the anti-platelet drugs. Single nucleotide polymorphism of CYP3A4 gene 894C〉T was detected with PCR and microarray technique. The number of coronary artery lesions was determined by PCI and the Gensini score was calculated. The patients were followed up for 3-12 months after discharge. Results No significant difference was found in CYP3A4 gene polymorphism between patients with clopidogrel resistance （CR group） and those without CR （NCR group） （P〉0.05）. Multivariate logistic regression analysis showed that CYP3A4 gene 894C〉T polymorphism was not correlated with CR in patients with ACS （OR 1.359, P〉0.05）. During the follow-up, the incidence of cardiovascular events was significantly higher in CR group than in NCR group （P〈0.05）, but this difference was not related to the mutation type of 894C〉T locus of CYP3A4 gene. Conclusion The CYP3A4 gene 894C〉T polymorphism is not associated with the effect of anti-ptatelet therapy and the risk of cardiovascular event in patients with ACS following PCI.