TY - JOUR

T1 - Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma

AU - Zolotareva, Karina

AU - Dotsenko, Polina A.

AU - Podkolodnyy, Nikolay

AU - Ivanov, Roman

AU - Makarova, Aelita Luiza

AU - Chadaeva, Irina

AU - Bogomolov, Anton

AU - Demenkov, Pavel S.

AU - Ivanisenko, Vladimir

AU - Oshchepkov, Dmitry

AU - Ponomarenko, Mikhail

N1 - This study was supported by the Russian Federal Science and Technology Program for the Development of Genetic Technologies.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

KW - SNP

KW - TATA box

KW - TBP

KW - candidate SNP marker

KW - gene

KW - gene expression change

KW - human

KW - in silico verification

KW - natural selection

KW - phylostratigraphic age

KW - primary open-angle glaucoma

KW - promoter

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85211801914&origin=inward&txGid=be44c3f303ecc74978df501422ae2126

UR - https://www.mendeley.com/catalogue/46b87f3c-30d1-31aa-9f2e-d6ca60cf5fe4/

U2 - 10.3390/ijms252312802

DO - 10.3390/ijms252312802

M3 - Article

C2 - 39684516

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 23

M1 - 12802

ER -