NOTCH信号通路基因在主动脉瓣狭窄遗传易感性中的作用
The Role of NOTCH Pathway Genes in the Inherited Susceptibility to Aortic Stenosis.
作者信息
Irtyuga Olga, Skitchenko Rostislav, Babakekhyan Mary, Usoltsev Dmitrii, Tarnovskaya Svetlana, Malashicheva Anna, Fomicheva Yulya, Rotar Oksana, Moiseeva Olga, Shadrina Ulyana, Artomov Mykyta, Kostareva Anna, Shlyakhto Evgeny
机构信息
Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia.
Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.
出版信息
J Cardiovasc Dev Dis. 2024 Jul 17;11(7):226. doi: 10.3390/jcdd11070226.
The NOTCH-signaling pathway is responsible for intercellular interactions and cell fate commitment. Recently, NOTCH pathway genes were demonstrated to play an important role in aortic valve development, leading to an increased calcified aortic valve disease (CAVD) later in life. Here, we further investigate the association between genetic variants in the NOTCH pathway genes and aortic stenosis in a case-control study of 90 CAVD cases and 4723 controls using target panel sequencing of full-length 20 genes from a NOTCH-related pathway (, , , , , , , , , , , , , , , , , , , ). We identified a common intronic variant in , protecting against CAVD development (rs3812603), as well as several rare and unique new variants in NOTCH-pathway genes (, , , , , , ), with a prominent effect of the protein structure and function.
NOTCH信号通路负责细胞间相互作用和细胞命运决定。最近，NOTCH通路基因被证明在主动脉瓣发育中起重要作用，导致晚年钙化性主动脉瓣疾病（CAVD）增加。在此，我们在一项病例对照研究中，对90例CAVD病例和4723例对照进行了NOTCH相关通路20个全长基因的靶向测序，进一步研究NOTCH通路基因中的遗传变异与主动脉瓣狭窄之间的关联。我们在NOTCH1中鉴定出一个常见的内含子变异（rs3812603），可预防CAVD的发生，以及NOTCH通路基因中的几个罕见且独特的新变异，对蛋白质结构和功能有显著影响。
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