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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 polymorphism and the risk of recurrent cardiac events after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). Methods A total of 275 ACS patients undergoing standard dual antiplatelet therapy and PCI were enrolled. Each patient’s platelet aggregation (PAR) was measured before and 7 days after taking antiplatelet drugs. Genotypes and alleles of CYP3A4 894C> T SNP in each group were determined by gene chip and PCR. The number of patients with coronary lesions was determined by PCI and their Gensini scores were calculated. Follow-up 3 to 12 months after discharge. Results CYP3A4 gene polymorphism in the clopidogrel resistance (CR) group and non-clopidogrel resistance (NCR) group, the difference was not statistically significant (P> 0.05). Multivariate Logistic regression analysis showed that there was no significant difference in the association of T mutation in CYP3A4 gene 894C> T locus with CR in patients with ACS (OR1.359, P> 0.05). After 3 to 12 months of follow-up, the incidence of cardiovascular events in CR group was higher than that in NCR group (P <0.05), but not with the mutation type of CYP3A4 gene at 894C> T site. Conclusion The polymorphism of CYP3A4 gene 894C> T locus has no clear guiding significance for antiplatelet effect and cardiovascular risk in ACS patients after PCI.