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首页> 外文期刊>Scientific reports. >The impact of P2Y12 promoter DNA methylation on the recurrence of ischemic events in Chinese patients with ischemic cerebrovascular disease
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The impact of P2Y12 promoter DNA methylation on the recurrence of ischemic events in Chinese patients with ischemic cerebrovascular disease

机译：P2Y12启动子DNA甲基化对中国缺血性脑血管病患者缺血事件复发的影响

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The primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P?=?0.018; ADP-induced platelet-fibrin clot strength (MAADP): P?=?0.030]. The concentrations of clopidogrel active metabolite had no significant difference (P?=?0.281). Sixteen CpG dinucleotides on P2Y12 promoter were tested. Three CpG sites (CpG11 and CpG12?+?13) showed lower methylation status, which correlated with a strong association with increased risk of clinical events. Changes of MAADP and ADP% were also associated with methylation levels of CpG 11 and CpG 12?+?13. Hypomethylation of the P2Y12 promoter is associated with a higher platelet reactivity and increased risk of ischemic events in our patients. Methylation analysis of peripheral blood samples might be a novel molecular marker to help early identification of patients at high risk for clinical ischemic events.
机译：氯吡格雷抗性的主要机制仍不清楚。我们旨在探讨P2Y12启动子的甲基化状态是否对血小板函数和临床缺血事件具有影响。患有缺血性脑血管疾病的患者注册了我们的研究。吸引静脉血液样品进行血栓血糖（TEG）和活性代谢物测定。患者基于一年后的缺血事件发生，分为病例或对照组。案例和对照组之间的两个TEG参数在统计学上显着[ADP抑制率（ADP％）：P？= 0.018; ADP诱导的血小板纤维蛋白凝块强度（MAADP）：P？= 0.030]。氯吡格雷活性代谢物的浓度无显着差异（P？= 0.281）。对P2Y12启动子的十六个CpG二核苷酸进行了测试。三个CPG位点（CPG11和CPG12？+ 13）显示较低的甲基化状态，与临床事件的风险增加相关。 MAADP和ADP％的变化也与CPG 11和CPG 12的甲基化水平有关？+？13。 P2Y12启动子的低甲基化与血小板反应性和患者缺血事件的风险增加有关。外周血样品的甲基化分析可能是一种新的分子标记，以帮助早期鉴定高风险临床缺血事件的患者。

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