The Role of NOTCH Pathway Genes in the Inherited Susceptibility to Aortic Stenosis.
Olga IrtyugaRostislav K SkitchenkoMary BabakekhyanDmitrii UsoltsevSvetlana TarnovskayaAnna MalashichevaYulya FomichevaOksana RotarOlga MoiseevaUlyana ShadrinaMykyta ArtomovAnna KostarevaEvgeny ShlyakhtoPublished in: Journal of cardiovascular development and disease (2024)
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.
Keyphrases
- aortic valve
- aortic stenosis
- transcatheter aortic valve replacement
- cell proliferation
- aortic valve replacement
- transcatheter aortic valve implantation
- ejection fraction
- genome wide
- left ventricular
- signaling pathway
- coronary artery disease
- bioinformatics analysis
- cell fate
- pi k akt
- oxidative stress
- transcription factor
- amino acid