P2RY1 and P2RY12 polymorphisms and on-aspirin platelet reactivity in patients with coronary artery disease

Int J Lab Hematol. 2012 Oct;34(5):473-83. doi: 10.1111/j.1751-553X.2012.01420.x. Epub 2012 May 10.

Abstract

Introduction: Association of P2RY1 and P2RY12 polymorphisms with on-aspirin platelet reactivity was investigated.

Materials and methods: Platelet reactivity was assessed by the light transmission aggregometry and TxB(2) assay in 423 patients with coronary artery disease (CAD) on aspirin. High residual platelet reactivity (RPR) was defined by ≥20% and ≥70% maximal aggregation stimulated with 0.5 mg/mL arachidonic acid (AA) and 10 μm ADP, respectively. Moderate RPR was considered aggregation ≥20% with AA, ≥70% with ADP, or ≥1 ng/mL stimulated TxB(2) . Fourteen P2RY1 and 35 P2RY12 single nucleotide polymorphisms (SNPs) were genotyped.

Results: High RPR was detected in 24% of the patients. Moderate RPR was observed in 31% with AA, 57% with 5 μm ADP, and 82% with 10 μm ADP. Stimulated TxB(2) was ≥1 ng/mL in 23% of patients. P2RY12 SNP rs9859538 was associated with high RPR (OR = 2.16, 95% CI = 1.24-3.75, P-value = 0.004). Four P2RY12 SNPs, rs1491974, rs10513398, rs3732765, and rs10935841, showed association with moderate RPR (OR = 1.79-2.94, P-value = 0.04-0.028), while five, rs7615865, rs1388623, rs1388622, rs7634096, and rs7637803, were associated with low RPR (OR = 0.50-0.55, P-value = 0.008-0.026), following ADP stimulation. TxB(2) level <1 ng/mL was linked to five P2RY1 SNPs, rs1439010, rs1371097, rs701265, rs12497578, and rs2312265 (OR = 0.36-0.54, P-value = 0.003-0.039).

Conclusions: Polymorphisms in P2RY1 and P2RY12 are associated with on-aspirin platelet reactivity in patients with CAD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aspirin / therapeutic use*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Function Tests
  • Polymorphism, Single Nucleotide*
  • Receptors, Purinergic P2Y1 / genetics*
  • Receptors, Purinergic P2Y12 / genetics*

Substances

  • P2RY1 protein, human
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2Y1
  • Receptors, Purinergic P2Y12
  • Aspirin