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

Abstract

Association of P2RY1 and P2RY12 polymorphisms with on-aspirin platelet reactivity was investigated. 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. 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). Polymorphisms in P2RY1 and P2RY12 are associated with on-aspirin platelet reactivity in patients with CAD.