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

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 TxB2 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 0.5mg/mL arachidonic acid (AA) and 10μm ADP, respectively. Moderate RPR was considered aggregation ≥20% with AA, ≥70% with ADP, or ≥1ng/mL stimulated TxB2. 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 5μm ADP, and 82% with 10μm ADP. Stimulated TxB2 was ≥1ng/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. TxB2 level <1ng/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. © 2012 Blackwell Publishing Ltd.