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CD80 DNA methylation and single-nucleotide polymorphism associated with clopidogrel response: a whole-genome DNA

Pei-Yuan Song1,2,3, Mu-Peng Li1,2,3, Li-Ming Peng1,2,3,4

  • 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.

Research and Practice in Thrombosis and Haemostasis
|March 27, 2023
PubMed

Insights

High on-treatment platelet reactivity (HTPR) after clopidogrel therapy is linked to DNA methylation changes. The CD80 gene

Area of Science:

  • Genomics and Epigenetics
  • Pharmacogenomics
  • Cardiovascular Medicine

Background:

  • Dual antiplatelet therapy (clopidogrel and aspirin) is standard post-percutaneous coronary intervention.
  • Interindividual variability in clopidogrel response, particularly high on-treatment platelet reactivity (HTPR), increases thrombotic event risk.

Purpose of the Study:

  • To investigate novel accessible factors, specifically DNA methylation, influencing clopidogrel response.
  • To identify potential biomarkers for predicting HTPR in patients undergoing percutaneous coronary intervention.

Main Methods:

  • DNA methylation levels were assessed using 850K bead chips.
  • Platelet reactivity index (PRI) was measured in 330 acute coronary syndrome (ACS) patients treated with clopidogrel.
  • Discovery and validation stages were employed to identify differential methylation loci (DMLs) and their association with HTPR.

Main Results:

  • 61 DMLs were identified between HTPR and non-HTPR groups, primarily in intergenic regions.
  • Lower CD80_cg06300880 methylation was observed in HTPR patients.
  • The rs34394661 AA genotype at the CD80_cg06300880 locus was associated with increased odds of HTPR and decreased methylation.
  • CYP2C19 poor metabolizers and the CD80_rs34394661 AA genotype were independent predictors of HTPR.

Conclusions:

  • CD80_cg06300880 methylation and the rs34394661 polymorphism are potential independent predictors of HTPR in clopidogrel therapy.
  • These findings may aid in personalized antiplatelet treatment strategies for ACS patients.
Abstract

Keywords:
DNA methylationacute coronary syndrome (ACS)clopidogrelplateletsingle-nucleotide polymorphism (SNP)

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