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

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.