The effects of polymorphisms in CYP2C19, ATP-binding cassette transporter B1, and paraoxonase-1 on clopidogrel treatment of Uygur patients following percutaneous coronary intervention

Abstract

Background

Acute coronary syndrome (ACS) carries a high mortality in Uygur populations. Percutaneous coronary intervention (PCI) is a safe treatment for patients with ACS. Clopidogrel reduces the risk for recurrent cardiovascular events after PCI; however, its activity is influenced by cytochrome P450 (CYP450), ATP-binding cassette transporter B1 (ABCB1), and paraoxonase-1 (PON1).

Objectives

To assess the effects of genetic polymorphisms CYP2C19*2, *3, *17, ABCB1 C3435T, and PON1 Q192R along with clinical and demographic factors on variations in responses in Uygur patients following PCI.

Methods

We enrolled 281 patients with PCI who were treated with clopidogrel and aspirin for at least 12 months and recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Approximately, 2 mL of peripheral venous blood samples were used for genotype detection. Binary logistic regression with likelihood ratio forward stepwise analysis and redundancy analysis were carried out to identify factors associated with MACE. We analyzed risk factors including age, body mass index, smoking, hypertension, dyslipidemia, gender, alcohol consumption, diabetes mellitus, carriers of ABCB1 C3435T T allele, carriers of PON1 Q192R A allele, metabolizer phenotype of CYP2C19, number of targeted vessels, and number of stents.

Results

The CYP2C19 IMs (OR 3.546, 95% CI 1.972–6.375, P = 0.001), CYP2C19 PMs (OR 7.038, 95% CI 1.658–29.880, P = 0.008), and number of targeted vessels (OR 2.033, 95% CI 1.078–3.648, P = 0.026) were significantly associated with MACE.

Conclusion

The CYP2C19 IMs, PMs, and the number of targeted vessels are essential factors associated with MACE risk in dual clopidogrel-treated Uygur population with ACS following PCI. These data provide valuable insights into the genetic polymorphisms affecting clopidogrel response among minority groups in China.

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Funding

The authors disclosed receipt of the following financial support for the research and/or publication of this article: This work was supported by 1.General program of Natural Science Foundation of Xinjiang Uygur Autonomous Region, Project No. 2018D01C108.;  2. Tianshan District Science and Technology Foundation of Urumqi, Xinjiang, Project No. T2017-07. 

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Authors

Contributions

Data curation: Tingting Wang, Hongjian Li, and Fengxia Wang. Formal analysis: Luhai Yu and Tingting Wang. Investigation: Luhai Yu and Hongjian Li. Project administration: Luhai Yu nd Hongjian Li. Validation: Li Sun and Fengxia Wang. Writing—original draft: Tingting Wang and Hongjian Li. Writing—review and editing: Luhai Yu and Li Sun.

Corresponding authors

Correspondence to Li Sun or Luhai Yu.

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The authors declare no competing interests.

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Wang, T., Li, H., Wang, F. et al. The effects of polymorphisms in CYP2C19, ATP-binding cassette transporter B1, and paraoxonase-1 on clopidogrel treatment of Uygur patients following percutaneous coronary intervention. Eur J Clin Pharmacol (2021). https://doi.org/10.1007/s00228-021-03176-z

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Keywords

  • CYP2C19
  • ABCB1
  • PON1
  • Clopidogrel
  • Percutaneous coronary intervention
  • Uygur