Genetic mutations in PEAR1 associated with cardiovascular outcomes in Chinese patients with acute coronary syndrome.

Objective: To investigate the association between PEAR1 (platelet endothelial aggregation receptor-1) polymorphisms and cardiovascular outcomes in acute coronary syndrome (ACS) in patients treated with aspirin and clopidogrel.

Methods: We genotyped eight common PEAR1 SNPs (rs2768759, rs12566888, rs12041331, rs11264579, rs2644592, rs822441, rs822442, and rs4661012), also CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) in 196 Chinese patients with ACS. We assessed the association between PEAR1 polymorphisms and platelet inhibition rate (PIR) measured by thromboelastography (TEG). The ischemic events over 12 months were recorded, and the relationship between PEAR1 polymorphisms and ischemic events was analyzed.

Results: Genetic mutations in rs822441, rs822442, and CYP2C192/3 alleles were significantly associated with a decrease in PIR induced by adenosine diphosphate (ADP). Carriers of the T allele in rs11264579 were less likely to have ischemic events compared with non-carriers (HR: 0.53, 95% CI: 0.30-0.94, P = .031). By contrast, carriers of the A allele in rs822442 had increased risk of ischemic events (HR: 1.82, 95% CI: 1.02-3.24, P = .043). However, these significant associations disappeared after controlling family-wise error rate.

Conclusions: For Chinese patients with ACS treated with aspirin and clopidogrel, genetic mutations in rs822441/rs822442 in PEAR1 correlated significantly with platelet activity after adjusting for CYP2C19 *2/*3 alleles. The rs11264579 T allele might be a protective factor for ischemic events; rs11264579, rs822441, and rs822442 might be genetic markers worthy of further research.