达比加特兰血水平的遗传决定因素及其与出血的关系
Guillaume Paré1, Niclas Eriksson, Thorsten Lehr
1Population Health Research Institute, Hamilton Health Sciences and McMaster University, David Braley Cardiac Vascular and Stroke Research Institute, 237 Barton St E, Room C3-103, Hamilton, ON, Canada L8L 2X2. pareg@McMaster.ca
Circulation
|March 8, 2013
概括
遗传变异影响达比加特兰度和出血风险. CES1 rs2244613多态性与心房患者的药物暴露率降低和出血事件减少有关.
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
- 遗传学 是一个遗传学.
背景情况:
- 与华法林相比,达比加乙酸可有效预防心房动的中风,具有良好的安全性.
- 达比加特兰度的个体间变化表明遗传因素的作用.
- 研究遗传影响可以优化达比加特兰疗法和患者的治疗结果.
研究的目的:
- 确定与达比加特兰度和临床结果相关的遗传变异.
- 探索基因变异对达比加特兰安全性和有效性的影响.
- 了解对达比加特兰治疗反应的个体间差异.
主要方法:
- 全基因组关联研究 (GWAS) 在长期抗凝治疗 (RE-LY) 随机评估试验的2944名参与者中进行.
- 单核酸多态 (SNP) 的分析,包括CES1 rs2244613,ABCB1 rs4148738,CES1 rs8192935.
- 统计评估基因变异之间的关联,达比加的低谷和高峰度,以及出血/缺血事件.
主要成果:
- CES1 SNP rs2244613与较低的达比加特兰最低度和降低任何出血风险显著相关.
- 携带CES1 rs2244613小等位基因 (32.8%的患者) 与每个等位基因的最低度下降15%相关.
- 与华法林相比,CES1 rs2244613小等位基因的携带者在达比加特兰治疗时经历的出血明显减少.
- 研究的遗传变异和缺血事件之间没有发现显著的关联.
结论:
- CES1 rs2244613的多态性是达比加特兰暴露和出血风险的关键决定因素.
- 基因分析,特别是CES1 rs2244613的基因分析,可能有助于个性化达比加特兰治疗.
- 这些发现支持药物基因组学在优化抗凝剂治疗策略中的作用.
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