The Role of NOTCH Pathway Genes in the Inherited Susceptibility to Aortic Stenosis.

IF 2.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiovascular Development and Disease Pub Date : 2024-07-17 DOI:10.3390/jcdd11070226

Olga Irtyuga, Rostislav Skitchenko, Mary Babakekhyan, Dmitrii Usoltsev, Svetlana Tarnovskaya, Anna Malashicheva, Yulya Fomicheva, Oksana Rotar, Olga Moiseeva, Ulyana Shadrina, Mykyta Artomov, Anna Kostareva, Evgeny Shlyakhto

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Abstract

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 (DVL2, DTX2, MFNG, NUMBL, LFNG, DVL1, DTX4, APH1A, DTX1, APH1B, NOTCH1, ADAM17, DVL3, NCSTN, DTX3L, ILK, RFNG, DTX3, NOTCH4, PSENEN). We identified a common intronic variant in NOTCH1, protecting against CAVD development (rs3812603), as well as several rare and unique new variants in NOTCH-pathway genes (DTX4, NOTCH1, DTX1, DVL2, NOTCH1, DTX3L, DVL3), with a prominent effect of the protein structure and function.

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NOTCH 通路基因在主动脉狭窄遗传易感性中的作用。

NOTCH信号通路负责细胞间相互作用和细胞命运承诺。最近，NOTCH 通路基因被证实在主动脉瓣发育过程中起着重要作用，并导致日后钙化性主动脉瓣病（CAVD）的增加。在此，我们通过对 NOTCH 相关通路的 20 个全长基因（DVL2、dtx2, mfng, numbl, lfng, dvl1, dtx4, aph1a, dtx1, aph1b, notch1, adam17, dvl3, ncstn, dtx3l, ilk, rfng, dtx3, notch4, psenen）。我们在 NOTCH1 基因中发现了一个常见的内含子变异，可防止 CAVD 的发生（rs3812603），还在 NOTCH 途径基因（DTX4、NOTCH1、DTX1、DVL2、NOTCH1、DTX3L、DVL3）中发现了几个罕见和独特的新变异，对蛋白质的结构和功能有显著影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cardiovascular Development and Disease CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

2.60

自引率

12.50%

发文量

381