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PXR polymorphisms have impact on the clinical efficacy of clopidogrel in patients undergoing percutaneous coronary

Yan Wu1, Hua Yu2, Hai-Qin Tang3

  • 1Department of Pharmacy, Anhui Provincial Hospital, Hefei, China; Department of Pharmacy, the First Affiliated Hospital of Anhui Medical University, Hefei, China.

Gene
|February 13, 2018
PubMed

Insights

Genetic variations in the pregnane X receptor (PXR) influence clopidogrel treatment effectiveness in patients undergoing percutaneous coronary intervention (PCI). Specific PXR polymorphisms are linked to major adverse cardiovascular events (MACE) after PCI.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Genetics

Background:

  • Clopidogrel is a key antiplatelet medication for Coronary Heart Disease (CHD) patients post-percutaneous coronary intervention (PCI).
  • Clopidogrel response variability (CRV) impacts clinical outcomes, with genetic factors playing a significant role.
  • The pregnane X receptor (PXR, NR1I2) is implicated in drug metabolism and response.

Purpose of the Study:

  • To investigate the association between PXR genetic polymorphisms and the clinical efficacy of clopidogrel in PCI patients.
  • To determine if specific PXR gene variants influence the risk of thrombotic events or other adverse outcomes.

Main Methods:

  • 384 patients undergoing PCI and treated with dual antiplatelet therapy (DAPT) were enrolled.
  • Plasma clopidogrel carboxylic acid metabolites (CLPM) and platelet maximum aggregation rate (MAR) were measured.
  • PXR genetic polymorphisms (rs3814057, rs3814058, rs6785049) and haplotypes were analyzed using Sequenom MassArray.
  • Clinical outcomes, including major adverse cardiovascular events (MACE) and bleeding, were monitored for 12 months post-PCI.

Main Results:

  • 153 patients experienced MACE, and 29 had bleeding events within 12 months.
  • PXR polymorphisms rs3814057, rs3814058, and rs6785049 were significantly associated with MACE risk.
  • Haplotype h1 (GCC) correlated with increased MACE risk, while haplotype h2 (AAT) was associated with a reduced risk.

Conclusions:

  • Specific genotypes and haplotypes of PXR (rs3814057, rs3814058, rs6785049) significantly impact the occurrence of MACE in clopidogrel-treated patients post-PCI.
  • These findings highlight the role of PXR genetics in clopidogrel pharmacogenomics and clinical outcomes.
  • PXR genetic variations may serve as predictive markers for clopidogrel efficacy in PCI patients.
Abstract

Keywords:
ClopidogrelMajor adverse cardiac eventNR1I2PXRPercutaneous coronary interventionPolymorphism

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