Associations of P2Y12R gene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel

Cardiovasc Ther. 2016 Dec;34(6):460-467. doi: 10.1111/1755-5922.12223.

Abstract

Objective: To investigate the correlations of three P2Y12 receptor (P2Y12R) gene polymorphisms (rs7428575 T>G, rs2046934 C>T, and rs3732759 A>G) with susceptibility to coronary artery disease (CHD) and clinical efficacy of clopidogrel treatment for CHD.

Methods: From May 2014 to May 2015, 178 CHD patients (the case group) and 182 healthy controls (the control group) were selected from our hospital. The platelet-rich plasma (PRP) turbidimetry was used to measure the rate of adenosine diphosphate (ADP)-induced platelet aggregation before and after clopidogrel treatment. Clopidogrel-sensitive group was defined as a 10% or greater decrease in the rate of platelet aggregation after 10 days of clopidogrel treatment, while clopidogrel-resistant group was defined as a <10% decrease. Genotyping was performed by denaturing high-performance liquid chromatography (DHPLC). A haplotype analysis of P2Y12R gene polymorphisms was performed using SHEsis software.

Results: There were significant differences in genotype and allele frequencies of rs2046934 C>T and rs3732759 A>G between the case and control groups (all P<.05). Haplotypes GTA and TTA were negatively associated with CHD risk (both P<.05), but haplotype TCA was positively associated with CHD risk (P=.005). CHD patients in the clopidogrel-sensitive group had higher frequencies of TT genotype of rs2046934 C>T and lower frequencies of GG genotype of rs3732759 A>G than those in the clopidogrel-resistant group (both P<.05).

Conclusions: P2Y12R gene rs2046934 C>T and rs3732759 A>G polymorphisms might be associated with the risk of CHD and the efficacy of clopidogrel treatment for CHD.

Keywords: P2Y12R; Clopidogrel; Coronary heart disease; Efficacy; Gene polymorphisms; Susceptibility.

MeSH terms

  • Aged
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Clopidogrel
  • Coronary Disease / blood
  • Coronary Disease / diagnosis
  • Coronary Disease / drug therapy*
  • Coronary Disease / genetics*
  • Drug Resistance
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Phenotype
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Polymorphism, Single Nucleotide*
  • Receptors, Purinergic P2Y12 / blood
  • Receptors, Purinergic P2Y12 / drug effects*
  • Receptors, Purinergic P2Y12 / genetics*
  • Risk Factors
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Ticlopidine