Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are...

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Published in:International journal of molecular sciences 2024-11, Vol.25 (23), p.12802
Main Authors: Zolotareva, Karina, Dotsenko, Polina A, Podkolodnyy, Nikolay, Ivanov, Roman, Makarova, Aelita-Luiza, Chadaeva, Irina, Bogomolov, Anton, Demenkov, Pavel S, Ivanisenko, Vladimir, Oshchepkov, Dmitry, Ponomarenko, Mikhail
Format: Article
Language:English
Subjects:
Age
Automation
Databases, Genetic
Disease
Exercise
Genes
Genetic Predisposition to Disease
Genomes
Glaucoma
Glaucoma, Open-Angle - genetics
Humans
Hypertension
Internet service providers
Optic nerve
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Proteins
Software packages
TATA-Box Binding Protein - genetics
TATA-Box Binding Protein - metabolism
Taxonomy
Tuberculosis
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Summary:Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes' promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services-PANTHER, DAVID, STRING, MetaScape, and GeneMANIA-as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms252312802