title: P2RY1 and P2RY12 polymorphisms and on-aspirin platelet reactivity in patients with coronary artery disease.
abstract: BACKGROUND
  Association of P2RY1 and P2RY12 polymorphisms with on-aspirin platelet reactivity was investigated.
  
  
  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.
authors.affiliation: Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Timur
authors.forename: G
authors.initials: G
authors.lastname: Murugesan
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: P P
authors.initials: PP
authors.lastname: Aung
authors.forename: J
authors.initials: J
authors.lastname: Barnard
authors.forename: Q K
authors.initials: QK
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Gaussem
authors.forename: R L
authors.initials: RL
authors.lastname: Silverstein
authors.forename: D L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: K
authors.initials: K
authors.lastname: Kottke-Marchant
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*
chemical_list: C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D001241:Aspirin