Department of Medicine, Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Clin Pharmacol Ther. 2020 Dec;108(6):1289-1298. doi: 10.1002/cpt.1959. Epub 2020 Jul 20.
The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post hoc analysis of 13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years. Participants had no previous diagnosis of atherothrombotic cardiovascular disease at enrollment, and were randomized to either 100 mg daily low-dose aspirin or placebo for median 4.7 years follow-up. We used Cox proportional hazard regression to model the relationship between rs12041331 and the ASPREE primary cardiovascular disease (CVD) end point, and composites of major adverse cardiovascular events (MACE) and ischemic stroke (STROKE); and bleeding events; major hemorrhage (MHEM) and intracranial bleeding (ICB). We performed whole-population analysis using additive and dominant inheritance models, then stratified by treatment group. Interaction effects between genotypes and treatment group were examined. We observed no statistically significant association (P < 0.05) in the population, or by treatment group, between rs12041331 and cardiovascular or bleeding events in either model. We also found no significant interaction effects between rs12041331-A and treatment group, for CVD (P = 0.65), MACE (P = 0.32), STROKE (P = 0.56), MHEM (P = 0.59), or ICB (P = 0.56). The genetic variant PEAR1 rs12041331 is not associated with cardiovascular events in response to low-dose aspirin in a healthy elderly population.
血小板内皮聚集受体-1（PEAR1）rs12041331 变体已被确定为血小板对包括阿司匹林在内的抗血小板治疗反应的遗传决定因素。然而，与动脉血栓形成性心血管事件的关联尚不清楚，大型试验的证据有限。在这里，我们在健康老年人的随机试验人群中测试了 rs12041331 与心血管事件和阿司匹林使用的相关性。我们对 ASPirin in Reducing Events in the Elderly（ASPREE）试验的 13547 名参与者进行了事后分析，中位年龄为 74 岁。参与者在入组时没有动脉血栓形成性心血管疾病的既往诊断，并且随机分配接受每天 100mg 低剂量阿司匹林或安慰剂治疗，中位随访时间为 4.7 年。我们使用 Cox 比例风险回归模型来模拟 rs12041331 与 ASPREE 主要心血管疾病（CVD）终点以及主要不良心血管事件（MACE）和缺血性中风（STROKE）的复合终点；以及出血事件；大出血（MHEM）和颅内出血（ICB）之间的关系。我们使用加性和显性遗传模型进行全人群分析，然后按治疗组分层。检查了基因型和治疗组之间的交互作用效应。我们在人群中或在任何模型中均未观察到 rs12041331 与心血管或出血事件之间具有统计学意义的关联（P<0.05），也未观察到 rs12041331-A 与治疗组之间存在显著的相互作用效应，无论是对于 CVD（P=0.65）、MACE（P=0.32）、STROKE（P=0.56）、MHEM（P=0.59）还是 ICB（P=0.56）。在健康老年人群中，血小板内皮聚集受体-1（PEAR1）rs12041331 变体与低剂量阿司匹林治疗后的心血管事件无关。
