The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-4329
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2026
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Eliseeva N.V.

Belgorod State National Research University

Ponomarenko I.V.

Belgorod State National Research University

Churnosov M.I.

Belgorod State National Research University

Analysis of the functional role of polymorphism in the CDKN2B-AS1 gene GWAS-significant for primary open-angle glaucoma (an in-silico study)

Authors:

Eliseeva N.V., Ponomarenko I.V., Churnosov M.I.

More about the authors

Journal: Russian Annals of Ophthalmology. 2021;137(4): 43‑50

DOI: 10.17116/oftalma202113704143

Read: 2140 times

Download PDF (RU)
Contact the author
Table of contents

ANALYSIS OF THE FUNCTIONAL ROLE OF POLYMORPHISM IN THE CDKN2B-AS1 GENE GWAS-SIGNIFICANT FOR PRIMARY OPEN-ANGLE GLAUCOMA (AN IN-SILICO STUDY)
ANALYSIS OF THE FUNCTIONAL ROLE OF POLYMORPHISM IN THE CDKN2B-AS1 GENE GWAS-SIGNIFICANT FOR PRIMARY OPEN-ANGLE GLAUCOMA (AN IN-SILICO STUDY)

To cite this article:

Eliseeva NV, Ponomarenko IV, Churnosov MI. Analysis of the functional role of polymorphism in the CDKN2B-AS1 gene GWAS-significant for primary open-angle glaucoma (an in-silico study). Russian Annals of Ophthalmology. 2021;137(4):43‑50. (In Russ.)
https://doi.org/10.17116/oftalma202113704143

Подписка 2026 Вестник офтальмологии (Russian Annals of Ophthalmology)
МСФ на ЯМ
Использование инфографики авторами научных работ
Close metadata
Recommended articles:
Modern approaches to combined surgery for cata­ract and primary open-angle glaucoma. Russian Annals of Ophthalmology. 2025;(3):92-99
Features of daily patterns of blood flow para­meters in the inte­rnal caro­tid arte­ries in primary open-angle glaucoma. Russian Annals of Ophthalmology. 2025;(5):66-71
Prevalence of low-functioning alle­les of folate cycle genes and their asso­ciation with cardiovascular pathology and a complicated obstetric history in the popu­lation of the Arkhangelsk Region. Labo­ratory Service. 2025;(3):8-13
Coro­naviruses in human pathophysiology: a brief history of the COVID-19 pandemic. Mole­cular Gene­tics, Microbiology and Viro­logy. 2025;(4-2):55-63
Distal 18q dele­tion syndrome (18q-) in a pediatric patient. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(12):244-248
Abstract:

Primary open-angle glaucoma (POAG) is the most common form of glaucoma in which genetic factors play a significant role. According to genome-wide studies (GWAS), the CDKN2B-AS1 gene is associated with POAG.

PURPOSE

To study in silico the functional significance of the CDKN2B-AS1 gene polymorphism GWAS-significant for primary open-angle glaucoma.

MATERIAL AND METHODS

The in-silico analysis was based on data from the GWAS catalog, five polymorphic loci of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) associated with POAG were selected. The study evaluated the regulatory potential, the relationship with the expression and alternative splicing of genes of the CDKN2B-AS1 gene polymorphism using modern databases for functional genomics — HaploReg and GTExportal.

RESULTS

An important functional significance of the polymorphic loci rs1063192, rs7865618, rs2157719, rs944800, rs4977756 of the CDKN2B-AS1 gene was revealed. These loci are located in the region of histones marking enhancers and in the region of hypersensitivity to DNAse-1, can be found in more than ten different organs and tissues, in the regions of regulatory DNA motifs to five transcription factors (AIRE, GATA, Tgif1, Pou2f2, and Zfp187), and are associated with expression of three genes (CDKN2B-AS1, CDKN2B, CDKN2A) and alternative splicing of transcripts of two genes (CDKN2B-AS1 and RP11-149I2.4) in cell cultures, organs and tissues with pathogenic significance for glaucoma development.

CONCLUSION

Polymorphism of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) has significant regulatory potential and is associated with the expression and alternative splicing of genes, which possibly underlies its association with primary open-angle glaucoma.

Keywords:

primary open-angle glaucoma
CDKN2B-AS1
polymorphism
functional significance

Authors:

Eliseeva N.V.

Belgorod State National Research University

Ponomarenko I.V.

Belgorod State National Research University

Churnosov M.I.

Belgorod State National Research University

Received:

24.02.2021

Accepted:

13.04.2021

Close metadata

References:

  1. Egorov EA. Nacional’noe rukovodstvo po glaukome: dlya praktikuyushchih vrachej [National Guidelines for Glaucoma: For Medical Practitioners]. Egorov E.A., Astahov Yu.S., Erichev V.P., eds. M.: GEOTAR-Media; 2015. (In Russ.).
  2. Starikova D, Ponomarenko I, Reshetnikov E, Dvornyk V, Churnosov M. Novel data about association of the functionally significant polymorphisms of the MMP-9 gene with exfoliation glaucoma in the Caucasian population of Central Russia. Ophthalmic Res. [published online ahead of print, 2020 Oct 23]. https://doi.org/10.1159/000512507
  3. Kirilenko MYu, Tikunova EB, Sirotina SS, Polonikov AV, Bushueva OYu, Churnosov MI. Study of the associations of genetic polymorphisms of growth factors with the development of primary open-angle glaucoma. Vestnik oftal’mologii. 2017;133(3):9-15. (In Russ.). https://doi.org/10.17116/oftalma201713339-15
  4. Tikunova E, Ovtcharova V, Reshetnikov E, et al. Genes of tumor necrosis factors and their receptors and the primary open angle glaucoma in the population of central Russia. Int J Ophthalmol. 2017;10(10):1490-1494.
  5. Shiga Y, Akiyama M, Nishiguchi KM, et al. Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. Hum Mol Genet. 2018;27(8):1486-149.  https://doi.org/10.1093/hmg/ddy053
  6. Eliseeva N, Ponomarenko I, Reshetnikov E, Dvornyk V, Churnosov M. The LOXL1 gene polymorphisms candidate for exfoliation glaucoma are also associated with a risk for primary open-angle glaucoma in a Caucasian population of Central Russia. Mol Vis. 2021.
  7. Svinareva DI. The contribution of gene-gene interactions of polymorphic loci of matrix metalloproteinases to susceptibility to primary open-angle glaucoma in men. Nauchnyye rezul’taty biomeditsinskikh issledovaniy = Research Results in Biomedicine. 2020;6(1):63-77. (In Russ.). https://doi.org/10.18413/2658-6533-2020-6-1-0-6
  8. Eliseeva NV, Churnosov MI. Genome-wide studies of primary open-angle glaucoma. Vestnik oftal’mologii. 2020;136(5):129-135. (In Russ.). https://doi.org/10.17116/oftalma2020136051129
  9. Osman W, Low SK, Takahashi A, Kubo M, Nakamura Y. A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma. Hum Mol Genet. 2012;21(12):2836-2842. https://doi.org/10.1093/hmg/dds103
  10. Ramdas WD, van Koolwijk LM, Ikram MK, et al. A genome-wide association study of optic disc parameters. PLoS Genet. 2010;6(6):e1000978. https://doi.org/10.1371/journal.pgen.1000978
  11. Nakano M, Ikeda Y, Tokuda Y, et al. Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese. PLoS One. 2012;7(3):e33389. https://doi.org/10.1371/journal.pone.0033389
  12. Springelkamp H, Höhn R, Mishra A, et al. Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun. 2014;5:4883.
  13. Springelkamp H, Mishra A, Hysi PG, et al. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology. Genet Epidemiol. 2015;39(3):207-216.  https://doi.org/10.1002/gepi.21886
  14. Wiggs JL, Yaspan DL, Hauser MA, et al. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS. Genet. 2012;8(4):e1002654. https://doi.org/10.1371/journal.pgen.1002654
  15. Li Z, Allingham RR, Nakano M, et al. A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet. 2015;24(13): 3880-3892. https://doi.org/10.1093/hmg/ddv128
  16. Springelkamp H, Iglesias AI, Mishra A, et al. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics. Hum Mol Genet. 2017;26:438-453. 
  17. Burdon KP, Macgregor S, Hewitt AW, et al. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nat Genet. 2011;43:574-578. 
  18. Charahkhani P, Burdon RK, Fogarty R, et al. Common variants near ABCA1,AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nat Genet. 2014;(10):1120-112.  https://doi.org/10.1038/ng.3079
  19. Ponomarenko I, Reshetnikov E, Altuchova O, et al. Association of genetic polymorphisms with age at menarche in Russian women. Gene. 2019;(686): 228-236. 
  20. Ward LD, Kellis M. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res. 2016;44(D1):877-881. 
  21. GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. 2020;369(6509):1318-1330. https://doi.org/10.1126/science.aaz1776
  22. Ponomarenko IV, Polonikov AV, Churnosov MI. Polymorphic LHCGR gene loci associated with the development of uterine fibroids. Akusherstvo i Ginekologiya = Obstetrics and Gynecology. 2018;(10):86-91. (In Russ.). https://doi.org/doi.orgaig.2018.10.86-91
  23. Ponomarenko IV, Reshetnikov EA, Polonikov AV, Churnosov MI. The polymorphic locus rs314276 of the LIN28B gene is associated with the age of menarche in women of the Central Black Earth Region of Russia. Akusherstvo i Ginekologiya = Obstetrics and Gynecology. 2019;(2):98-104. (In Russ.).
  24. Ponomarenko I, Reshetnikov E, Polonikov A, et al. Candidate genes for age at menarche are associated with endometrial hyperplasia. Gene. 2020;757: 144933. https://doi.org/10.1016/j.gene.2020.144933
  25. Ponomarenko I, Reshetnikov E, Polonikov A, et al. Candidate genes for age at menarche are associated with endometriosis. Reprod Biomed Online. 2020; 41(5):943-956.  https://doi.org/10.1016/j.rbmo.2020.04.016
  26. Ponomarenko I, Reshetnikov E, Polonikov A, et al. Candidate genes for age at menarche are associated with uterine leiomyoma. Front Genet. 2021;11: 512940. https://doi.org/10.3389/fgene.2020.512940
  27. Svinareva DI, Churnosov MI. The role of metalloproteinases in the development of primary open-angle glaucoma. Vestnik oftal’mologii. 2020;136(4): 146-150. (In Russ.). https://doi.org/10.17116/oftalma2020136041146
  28. Tham YC, Cheng CY. Associations between chronic systemic diseases and primary open angle glaucoma: an epidemiological perspective. Clin Exp Ophthalmol. 2017;45:24-32. 
Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.