外基组测序暗示SYNE1的祖先相关的门德尔变异在童年开始的基本高血压中存在
Ian Copeland1, Edmond Wonkam-Tingang2, Monesha Gupta-Malhotra3
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
JCI insight
|May 8, 2024
概括
SYNE1基因的罕见遗传变异与童年开始的基本高血压 (COEH) 有关,特别是在非洲血统的儿童中. 这一发现为COEH提供了新的见解.
科学领域:
- 遗传学和心血管疾病
- 儿科高血压研究研究
背景情况:
- 童年开始的基本高血压 (COEH) 在美国不成比例地影响着非洲血统的儿童.
- 尽管有遗传性和偏差的人口统计数据的证据,但COEH的遗传基础在很大程度上仍未知.
- 之前的研究还没有确定负责COEH的特定基因.
研究的目的:
- 为了确定与童年开始的基本高血压 (COEH) 相关的遗传变异.
- 研究SYNE1基因在COE.H.病原发生中的作用.
- 探索精密疗法在治疗COEH中的潜力.
主要方法:
- 对16个早期出现COEH的家族和另外48个COEH家族进行了外基因组测序.
- 分析包括1,700个内部三重组和公共数据集,以评估SYNE1的变化.
- 在体外研究中,在光滑肌肉血管细胞中利用SYNE1的shRNA淘汰来评估功能影响.
主要成果:
- 在16个COEH家族中,在3个COEH家族中发现了SYNE1基因的衰退性,罕见和可能有害的误解变异.
- 复合异构性SYNE1变异在COEH个体中显著丰富,特别是那些具有非洲遗传血统的个体.
- 减少SYNE1表达降低了血管光滑肌肉细胞弹性,通过RhoA/ROCK通路抑制可逆.
结论:
- 罕见的双性SYNE1变异与儿童开始的基本高血压 (COEH) 的分子遗传学有关.
- 这些发现揭示了一种新的病理生理学,涉及SYNE1和血管光滑肌肉细胞弹性.
- 这项研究表明,基于SYNE1遗传发现,可针对COEH进行向治疗.
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