通过血液蛋白质组的孟德尔随机化分析识别出缺血性中风的新药点
Michael Chong1,2, Jennifer Sjaarda1, Marie Pigeyre1
1Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Ontario, Canada (M.C., J.S., M.P., P.M.-S., R.L., A.S., H.C.G., G.P.).
Circulation
|June 19, 2019
概括
这项研究使用孟德尔随机化确定了缺血性中风的新型蛋白质生物标志物. 对于治疗心血管栓塞性中风而言,Scavenger受体A5类 (SCARA5) 是有前途的,没有预测的不良影响.
科学领域:
- 遗传学和基因组学
- 心血管研究
- 生物标志物发现
背景情况:
- 新的治疗目标对于治疗缺血性中风至关重要.
- 有遗传证据的循环蛋白生物标志物提供了潜在的药物标.
- 缺乏对中风生物标志物的系统查.
研究的目的:
- 确定与缺血性中风亚型有因果关系的循环蛋白生物标志物.
- 评估这些生物标志物对内出血的潜在副作用.
- 评估各种疾病中潜在的药物点的更广泛的安全性.
主要方法:
- 在653个循环蛋白质上使用孟德尔随机化 (MR) 分析.
- 评估了三种缺血性中风亚型的因果调解:大动脉动脉硬化,心性中风和小动脉封闭.
- 采用了包括MEGASTROKE和英国生物库在内的大规模全基因组关联研究 (GWAS) 数据.
主要成果:
- 确定了几种缺血性中风亚型的因果调解者,包括心血管栓塞性中风的SCARA5和TNFSF12.
- SCARA5和TNFSF12在心血管梗塞中发挥了保护作用,但TNFSF12增加了出血风险.
- 对于凝血因子XI,阿波利波蛋白和SCARA5没有预测的不良副作用.
结论:
- 一个系统的MR查发现了5个已确定的和2个新的缺血性中风生物标志物.
- 用于指导药物目标优先级的副作用概况.
- SCARA5已成为心性中风的有希望的治疗点,具有良好的安全性.
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