Correlation Between SNPs in Candidate Genes and VerifyNow-Detected Platelet Responsiveness to Aspirin and Clopidogrel Treatment

Cardiovasc Drugs Ther. 2015 Apr;29(2):137-46. doi: 10.1007/s10557-015-6585-6.

Abstract

Purpose: Patients with high on-treatment platelet reactivity (HPR) against aspirin or clopidogrel are at increased risk for adverse cardiovascular events. In this study, we explored the predictive value of common SNPs for the on-treatment platelet reactivity (OPR) against aspirin and clopidogrel assessed by VerifyNow assays.

Methods: This study recruited 286 Han Chinese individuals undergoing antiplatelet treatment, including 159 cases with aspirin only (100 mg/day) and 127 cases with dual therapy (aspirin 100 mg/day plus clopidogrel 75 mg/day) for at least 2 weeks. The OPR against aspirin and clopidogrel were assessed by VerifyNow Aspirin (ARU) and P2Y12 assays (PRU), respectively. Genotyping for the selected 25 SNPs within 11 genes and 2 GWAS loci was carried out by ABI multiplex SNaPshot method.

Results: The results indicated that rs4244285 (CYP2C19) and rs342293 (7q22.3) were significantly associated with PRU value (both P < 0.01). As for the OPR to aspirin, a weak statistical significance was observed in rs5445 (GNB3) (P = 0.049) and rs5758 (TBXA2R) (P = 0.045). After adjusting for the covariates including gender, age and smoking, carriers of allele A of rs4244285 remained as a strong predictor for HPR against clopidogrel.

Conclusion: The current study suggests that common SNPs may predict OPR against clopidogrel as assessed by VerifyNow P2Y12, but are less likely to respond against aspirin as assessed by VerifyNow Aspirin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation / genetics*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Polymorphism, Single Nucleotide*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin