罕见的破坏性CCR2变体与较低的终身心血管风险有关
Marios K Georgakis1,2,3, Rainer Malik4, Omar El Bounkari4
1Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University (LMU), Feodor-Lynen-Str. 17, 81377, Munich, Germany. marios.georgakis@med.uni-muenchen.de.
准参与单细胞运动的CCR2受体,可以预防动脉样硬化. 基因变异CCR2与心脏病发作和冠状动脉疾病的风险降低有关,而不会增加感染风险.
科学领域:
- 心血管遗传学 心血管遗传学
- 免疫学 免疫学 免疫学
- 药物基因组学 药物基因组学
背景情况:
- CCL2 (化基因) 涉及到动脉样硬化.
- 在人类动脉样硬化中准CCR2 (CCL2受体) 的作用尚不清楚.
研究的目的:
- 研究CCR2变异对动脉样硬化心血管疾病风险的影响.
- 评估针对CCR2.2的治疗潜力.
主要方法:
- 来自英国生物库参与者 (n=454,775) 的全外组测序数据被分析为CCR2变异.
- 基因负担测试发现了CCR2变体和心血管终点之间的关联.
- 功能性测试 (迁移,cAMP) 验证了优先变异的影响.
- 在六个独立队列 (n=1,062,595) 的复制证实了显著的关联.
主要成果:
- 具有破坏性CCR2变异的个体 (n=787) 患心肌梗塞和冠状动脉疾病的风险较低.
- 一种特定的变异 (M249K) 减少了单细胞数和CCL2信号.
- M249K与心肌梗塞和冠状动脉疾病的风险明显降低有关.
- 在M249K载体中没有观察到感染风险的增加.
结论:
- 经过实验验证的破坏性CCR2变异与心肌梗塞和冠状动脉疾病的终身风险较低有关.
- 针对CCR2的向显示出作为一种地球保护策略的前景.
- 遗传证据支持开发针对心血管疾病的CCR2向疗法.
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