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

Nan Fang Yi Ke Da Xue Xue Bao. 2016 Feb 20;37(2):261-265. doi: 10.3969/j.issn.1673-4254.2017.02.20.
[Article in Chinese]

Abstract

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-platelet therapy and the risk of cardiovascular event in patients with ACS following PCI.

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。

MeSH terms

  • Acute Coronary Syndrome / therapy*
  • Alleles
  • Blood Platelets
  • Clopidogrel
  • Cytochrome P-450 CYP3A / genetics*
  • Humans
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Polymorphism, Single Nucleotide
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Ticlopidine

Grants and funding

安徽省科技攻关项目(1501041154);安徽省高校自然科学研究重大项目(KJ2015ZD30);安徽省高校自然科学研究一般项目(KJ2015B003by)