School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Thromb Res. 2018 Mar;163:77-82. doi: 10.1016/j.thromres.2018.01.026. Epub 2018 Feb 2.
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.
We genotyped eight common PEAR1 SNPs (rs2768759, rs12566888, rs12041331, rs11264579, rs2644592, rs822441, rs822442, and rs4661012), also CYP2C192 (rs4244285) and CYP2C193 (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.
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.
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.
探讨血小板内皮聚集受体 1（PEAR1）多态性与阿司匹林和氯吡格雷治疗的急性冠脉综合征（ACS）患者心血管结局的关系。
我们对 196 例中国 ACS 患者的 8 个常见 PEAR1 SNPs（rs2768759、rs12566888、rs12041331、rs11264579、rs2644592、rs822441、rs822442 和 rs4661012）以及 CYP2C192（rs4244285）和 CYP2C193（rs4986893）进行基因分型。我们评估了 PEAR1 多态性与血栓弹力图（TEG）测量的血小板抑制率（PIR）之间的关系。记录了 12 个月内的缺血事件，并分析了 PEAR1 多态性与缺血事件之间的关系。
rs822441、rs822442 和 CYP2C192/3 等位基因的基因突变与二磷酸腺苷（ADP）诱导的 PIR 降低显著相关。与非携带者相比，rs11264579 中的 T 等位基因携带者发生缺血事件的可能性较小（HR：0.53，95%CI：0.30-0.94，P=0.031）。相比之下，rs822442 中的 A 等位基因携带者发生缺血事件的风险增加（HR：1.82，95%CI：1.02-3.24，P=0.043）。然而，在控制全错误率后，这些显著关联消失了。
对于接受阿司匹林和氯吡格雷治疗的中国 ACS 患者，PEAR1 中的 rs822441/rs822442 基因突变与 CYP2C19*2/*3 等位基因调整后的血小板活性显著相关。rs11264579 的 T 等位基因可能是缺血事件的保护因素；rs11264579、rs822441 和 rs822442 可能是值得进一步研究的遗传标记。
