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测量和基因预测白细胞端粒长度与血管表型的关联:基于人口的研究

Dan Liu¹, N Ahmad Aziz^1,2, Mohammed Aslam Imtiaz¹

¹German Center for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany.

|October 2, 2023

概括

较短的白细胞端粒长度 (LTL) 与心血管问题有关. 影响LTL的非遗传因素显著影响血管健康,表明潜在的干预目标.

科学领域:

遗传学和表观遗传学
心血管健康心血管健康
衰老研究研究衰老研究

背景情况:

白血球端粒长度 (LTL) 是一种与心血管功能障碍相关的生物标志物.
测量与基因预测的LTL对血管健康的差异影响尚不清楚.
将LTL与心血管健康联系起来的分子机制需要进一步阐明.

研究的目的:

研究测量和基因预测的LTL与血管功能的关联.
探索测量和基因预测LTL (ΔLTL) 之间的差异在血管健康中的作用.
确定与LTL和血管健康相关的分子途径,特别是表观遗传修饰.

主要方法:

利用了基于人口的莱研究队列的基线数据.
计算了4180名参与者的基因预测LTL,并通过qPCR测量了1828名参与者的LTL.
采用多变量回归和全表观基因组关联研究 (EWAS) 来分析LTL测量和血管功能.

主要成果:

测量较长的LTL与更好的微血管和心脏功能相关.
较长的基因预测LTL与心脏功能改善有关.
较大的DLTL独立地与增强的微血管功能,心脏功能和整体血管健康有关.
EWAS确定了与所有三种LTL测量相关的CpG位点,其中与DLTL相关的基因丰富在血管内皮信号通路中.

结论:

低血压的非遗传决定因素在微血管和心脏功能中起着至关重要的作用.
血管内皮信号通路的表观遗传修饰调解了LTL对血管健康的影响.
针对LTL的非遗传影响可能提供一种改善心血管健康的治疗策略.

关键词:

心脏功能是如何工作的整个表观基因组的关联.白血细胞端粒的长度是多少微血管功能微血管功能多基因风险评分多基因风险评分.

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