与阿司匹林和克洛皮多格雷尔耐药性相关的分子基因组和表观基因组特征
Jei Kim1,2, Byoung-Soo Shin3, Dae-Hyun Kim4
1Department of Neurology, College of Medicine and Hospital, Daejeon-Chungnam Regional Cardiocerebrovascular Disease Center, Chungnam National University, Daejeon, South Korea. jeikim@cnu.ac.kr.
基因组和表观基因组因素改善了对阿司匹林和克洛皮多格雷尔耐药性的预测. 这些发现提高了对中风患者耐药性和心血管风险预测的理解.
科学领域:
- 药物基因组学 药物基因组学
- 心血管医学 心血管医学
- 代谢学 代谢学 代谢学
背景情况:
- 抗阿司匹林和克洛皮多格雷尔耐药性与酸代谢媒介和基因变异有关.
- 克洛皮多格雷尔的肝脏激活也与耐药性有关.
- 当前的风险预测模型无法充分考虑这些因素.
研究的目的:
- 调查介质,基因组和表观基因组因素是否可以改善阿司匹林和克洛皮多格雷尔耐药性的预测.
- 评估这些因素与已确定的中风复发心血管风险的联合预测能力.
- 评估它们对实验室药物反应 (ARU和PRU) 的影响.
主要方法:
- 一项针对988名患有过渡性缺血性发作和缺血性中风的患者进行的前性队列研究.
- 评估阿司匹林反应单位 (ARU) 和P2Y12反应单位 (PRU) 来测量药物耐药性.
- 在阿拉基酸代谢和克洛皮多格雷尔激活途径中分析了介质,基因多态化和促进子甲基化.
主要成果:
- 用于复发预测的物流模型,增加了基因组/表观基因组变量,使灵敏度从3.4%提高到13.8%.
- 对ARU和PRU预测的线性模型显示,这些因素提高了性能 (ARU的R2=0.033,PRU的R2=0.210).
- 特定的基因型 (例如,TXAS1 rs41708,COX2 rs20417) 和甲基化模式被确定为重要的预测因素.
结论:
- 介导体,基因组和表观基因组特征协同增强了对阿司匹林和克洛皮多格雷尔耐药性的预测.
- 这些因素加上心血管风险,可以更好地预测缺血性中风的复发.
- 这些发现强调了个性化医疗方法在抗血小板治疗中的重要性.
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