Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.
Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.
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DOI：
10.1111/cts.12438
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Lewis JP
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文献类型：
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作者：
Backman JD;Yerges-Armstrong LM;Horenstein RB;Newcomer S;Shaub S;Morrisey M;Donnelly P;Drolet M;Tanner K;Pavlovich MA;O'Connell JR;Mitchell BD;Lewis JP
血小板内皮聚集受体1 （PEAR1）基因的遗传变异，尤其是rs12041331，与阿司匹林后血小板聚集改变和心血管事件风险增加有关。我们前瞻性地测试了常用处方剂量阿司匹林（81,162和324 mg/天）对67名健康个体rs12041331基因型激动剂诱导的血小板聚集的影响。在服用阿司匹林之前，与非携带者相比，rs12041331次要等位基因携带者显著降低了二磷酸腺苷（ADP）诱导的血小板聚集（P = 0.03），但与其他血小板途径无关。相比之下，当胶原蛋白和肾上腺素刺激血小板聚集时，rs12041331与非阿司匹林组血小板聚集显著相关（所有关联均P < 0.05），但与ADP无关。PEAR1 rs12041331对血小板聚集的影响是途径特异性的，并且在治疗剂量下被阿司匹林改变，但不是剂量依赖性的方式。需要进一步的研究来确定PEAR1对阿司匹林治疗患者心血管事件的影响。
Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on‐aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist‐induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly reduced adenosine diphosphate (ADP)‐induced platelet aggregation compared with noncarriers (P = 0.03) but was not associated with other platelet pathways. In contrast, rs12041331 was significantly associated with on‐aspirin platelet aggregation when collagen and epinephrine were used to stimulate platelet aggregation (P < 0.05 for all associations), but not ADP. The influence of PEAR1 rs12041331 on platelet aggregation is pathway‐specific and is altered by aspirin at therapeutic doses, but not in a dose‐dependent manner. Additional studies are needed to determine the impact of PEAR1 on cardiovascular events in aspirin‐treated patients.