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PEAR1, PON1, CYP2C19, CYP1A2 and F2R Polymorphisms are Associated with MACE in Clopidogrel-Treated Patients with

Pengqiang Du1, Xingang Li2, Dandan Li2

  • 1Department of Pharmacy, Fuwai Central China Cardiovascular Hospital, Henan Provincial People's Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, 450003, People's Republic of China.

Pharmacogenomics and Personalized Medicine
|December 26, 2024
PubMed

Insights

Genetic variations in PEAR1, PON1, CYP2C19, and CYP1A2 increase the risk of major adverse cardiovascular events (MACE) in patients treated with clopidogrel after percutaneous coronary intervention (PCI). Conversely, F2R gene variants are linked to reduced MACE risk.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Clopidogrel is a vital antiplatelet medication for acute coronary syndrome (ACS) patients post-percutaneous coronary intervention (PCI).
  • Individual responses to clopidogrel can vary due to genetic factors, influencing treatment efficacy and safety.
  • Understanding these genetic influences is crucial for optimizing antiplatelet therapy and preventing adverse events.

Purpose of the Study:

  • To investigate the association between clopidogrel-related gene polymorphisms and the incidence of recurrent thrombotic events and cardiovascular death in ACS patients undergoing PCI.
  • To identify specific genetic markers that predict treatment outcomes in patients receiving clopidogrel therapy.

Main Methods:

  • Genotype testing was performed for 26 loci across 18 genes associated with clopidogrel response in 200 ACS patients post-PCI.
  • Patients were on dual antiplatelet therapy including clopidogrel.
  • Major adverse cardiovascular events (MACE) and clinical endpoints were systematically documented and analyzed in relation to genetic polymorphisms.

Main Results:

  • Polymorphisms in PEAR1 (rs41273215), PON1 (rs662), CYP2C19 (rs4244285), and CYP1A2 (rs762551) were significantly associated with an increased risk of MACE.
  • Specifically, carriers of the T-allele for rs41273215 (PEAR1), rs662 (PON1), the A-allele for rs4244285 (CYP2C19), and the C-allele for rs762551 (CYP1A2) showed higher MACE rates.
  • Conversely, the variant T-allele of rs168753 (F2R) was associated with a significant reduction in MACE risk.

Conclusions:

  • Specific gene polymorphisms in PEAR1, PON1, CYP2C19, and CYP1A2 are linked to an elevated risk of MACE in patients undergoing PCI and treated with clopidogrel.
  • The F2R polymorphism (rs168753) appears to confer a protective effect, reducing the risk of adverse cardiovascular events.
  • Genotyping for these polymorphisms may aid in identifying high-risk patients, enabling personalized antiplatelet therapy strategies.
Abstract

Keywords:
MACEacute coronary syndromeclopidogrelpercutaneous coronary interventionsingle nucleotide polymorphism

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