Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study

BMC Cardiovasc Disord. 2021 Aug 12;21(1):391. doi: 10.1186/s12872-021-02201-4.

Abstract

Background: Acute coronary syndrome (ACS) has become a vital disease with high mortality in the Uygur populations. Clopidogrel plays an important role in reducing the risk of recurrent cardiovascular events after ACS; however, it is a prodrug that requires biotransformation by cytochrome P450 (CYP450).

Objectives: To determine the effect of genetic polymorphisms in CYP2C19*2, *3, and *17, and along with clinical, demographic factors, on variation in response to clinical outcomes in Uygur patients.

Methods: A total of 351 patients with ACS were treated with clopidogrel and aspirin for at least 12 months; we recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Multivariable logistic regression analyses were carried out to identify factors associated with MACE or bleeding.

Results: We analyze risk factors include age, BMI (body mass index), smoking, alcohol intake, NSTEMI (non-ST-segment elevation myocardial infarction), hypertension, dyslipidemia, concomitant medication, CYP2C19*2 carriers, CYP2C19*17 carriers and metabolizer phenotype. CYP2C19*2 carriers had an odds of having MACE of 2.51 (95% CI: 1.534-4.09) compared with noncarriers (P < .001). However, no factors were significantly associated with bleeding (P > 0.05).

Conclusion: The CYP2C19*2 gene polymorphism contributes to the risk of MACE in dual clopidogrel-treated Uygur population with ACS with or without PCI (percutaneous coronary intervention). These data may provide valuable insights into the genetic polymorphisms affecting clopidogrel metabolism among minority groups in China.

Keywords: Acute coronary syndrome; Bleeding; CYP2C19; Clopidogrel; Major adverse cardiovascular events; Uygur.

Publication types

  • Observational Study

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / ethnology
  • Adult
  • Aged
  • Aspirin / adverse effects
  • Aspirin / therapeutic use
  • Body Mass Index
  • Case-Control Studies
  • China / ethnology
  • Clopidogrel / adverse effects
  • Clopidogrel / metabolism
  • Clopidogrel / therapeutic use*
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Prodrugs / metabolism
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Prodrugs
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Aspirin