Xiao-Yan Nie1, Jun-Lei Li2, Si-Bei Qin2, Yu Fu2, Guang-Kai Liang2, Lu-Wen Shi2, Hong Shao2, Jian Liu3, Yun Lu4. 1. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: niexy@bjmu.edu.cn. 2. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. 3. Department of Cardiology, Peking University People's Hospital, Beijing 100044, China. Electronic address: drjianliu@163.com. 4. Department of Pharmacy, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
Abstract
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 CYP2C19⁎2/⁎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.
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 CYP2C19⁎2/⁎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.
Authors: Joshua P Lewis; Moeen Riaz; Sophia Xie; Galina Polekhina; Rory Wolfe; Mark Nelson; Andrew M Tonkin; Christopher M Reid; Anne M Murray; John J McNeil; Alan R Shuldiner; Paul Lacaze Journal: Clin Pharmacol Ther Date: 2020-07-20 Impact factor: 6.875
Authors: Benedetta Izzi; Francesco Gianfagna; Wen-Yi Yang; Katrien Cludts; Amalia De Curtis; Peter Verhamme; Augusto Di Castelnuovo; Chiara Cerletti; Maria Benedetta Donati; Giovanni de Gaetano; Jan A Staessen; Marc F Hoylaerts; Licia Iacoviello Journal: Clin Epigenetics Date: 2019-10-29 Impact factor: 6.551