Premium
P2RY1 and P2RY12 polymorphisms and on‐aspirin platelet reactivity in patients with coronary artery disease
Author(s) -
TIMUR A. A.,
MURUGESAN G.,
ZHANG L.,
AUNG P. P.,
BARNARD J.,
WANG Q. K.,
GAUSSEM P.,
SILVERSTEIN R. L.,
BHATT D. L.,
KOTTKEMARCHANT K.
Publication year - 2012
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/j.1751-553x.2012.01420.x
Subject(s) - coronary artery disease , single nucleotide polymorphism , aspirin , arachidonic acid , platelet , snp , medicine , gastroenterology , chemistry , genotype , biochemistry , enzyme , gene
Summary 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 μ m 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 μ m ADP, and 82% with 10 μ m 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.