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将多态性Rs12041331和Rs2768759用作轻度中风和短暂性脑缺血发作背景下90天出血事件的潜在预测标志物。

Using the Polymorphisms Rs12041331 and Rs2768759 as Potential Predictive Markers of 90-Day Bleeding Events in the Context of Minor Strokes and Transient Ischemic Attack.

作者信息

Xu Yanjie, Yao Dongxiao, Chen Weiqi, Yan Hongyi, Zhao Dexiu, Jiang Lingling, Wang Yicong, Zhao Xingquan, Liu Liping, Wang Yongjun, Pan Yuesong, Wang Yilong

机构信息

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100069, China.

China National Clinical Research Center for Neurological Diseases, Beijing 100070, China.

出版信息

Brain Sci. 2023 Sep 30;13(10):1404. doi: 10.3390/brainsci13101404.

Abstract

In this study, we explored the relationship between the platelet endothelial aggregation receptor 1 () polymorphisms, platelet reactivity, and clinical outcomes in patients with minor stroke or transient ischemic attack (TIA). Randomized controlled trial subgroups were assessed, wherein patients received dual antiplatelet therapy for at least 21 days. Platelet reactivity was measured at different time intervals. Genotypes were categorized as wild-type, mutant heterozygous, and mutant homozygous. Clinical outcomes were evaluated after 90 days. The rs12041331 polymorphism predominantly influenced adenosine diphosphate channel platelet activity, with the AA genotype displaying significantly lower residual platelet activity to the P2Y12 response unit ( < 0.01). This effect was more evident after 7 days of dual antiplatelet treatment ( = 0.016). Mutant A allele carriers had decreased rates of recurrent stroke and complex endpoint events but were more prone to bleeding ( = 0.015). The rs2768759 polymorphism majorly impacted arachidonic acid (AA) channel platelet activity, which was particularly noticeable in the C allele carriers. Our regression analysis demonstrated that rs12041331 AA + GA and rs2768759 CA predicted 90-day post-stroke bleeding. In conclusion, the polymorphisms rs12041331 and rs2768759 interfere with platelet aggregation and the performance of antiplatelet drugs. These genetic variations may contribute to bleeding events associated with minor stroke and TIA.

摘要

在本研究中,我们探讨了轻度卒中或短暂性脑缺血发作(TIA)患者的血小板内皮聚集受体1()基因多态性、血小板反应性与临床结局之间的关系。对随机对照试验亚组进行了评估,其中患者接受了至少21天的双联抗血小板治疗。在不同时间间隔测量血小板反应性。基因型分为野生型、突变杂合子和突变纯合子。90天后评估临床结局。rs12041331基因多态性主要影响二磷酸腺苷通道血小板活性,AA基因型对P2Y12反应单位的残余血小板活性显著降低(<0.01)。双联抗血小板治疗7天后,这种效应更为明显(=0.016)。突变A等位基因携带者复发性卒中和复合终点事件的发生率降低,但更容易出血(=0.015)。rs2768759基因多态性主要影响花生四烯酸(AA)通道血小板活性,这在C等位基因携带者中尤为明显。我们的回归分析表明,rs12041331 AA + GA和rs2768759 CA可预测卒中后90天出血。总之,rs12041331和rs2768759基因多态性会干扰血小板聚集和抗血小板药物的性能。这些基因变异可能导致与轻度卒中和TIA相关的出血事件。

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