DOI: 10.18413/2658-6533-2020-6-2-0-4

A replicative study of the associations of polymorphic loci of the LOXL1 and CDKN2B-AS1 genes with the development of primary open-angle glaucoma in men of the Central Black Earth Region of the Russian Federation

Background: Studying the genetic foundations of primary open-angle glaucoma (POAG) is an urgent task due to the fact that glaucoma is the main cause of low vision and blindness among people of working age. Over the past decade, full-genomic studies (GWAS) of primary open-angle glaucoma have revealed more than 150 candidate genes associated with the development of glaucoma. At the same time, replicative studies of GWAS-significant loci for POAG in various ethno-territorial groups are of great importance. The aim of the study: To conduct a replicative study of the association of GWAS-significant polymorphic loci of the LOXL1 and CDKN2B-AS1 genes with the development of primary open-angle glaucoma in men of the Central Black Earth Region of the Russian Federation. Materials and methods: The work was performed in the design of "patients-control." The study included 246 men with POAG and 176 people in the control group. The material for molecular genetics research was DNA isolated from the venous blood of the studied individuals using the standard method of phenol-chloroform extraction. GWAS polymorphic loci of the CDKN2B-AS1 genes (rs7865618, rs2157719, rs1063192, rs944800, rs4977756) and LOXL1 (rs893818, rs4886776) that were significant for POAG were selected for the study. Genotyping was carried out using the polymerase chain reaction of DNA synthesis by allele discrimination. Results: The polymorphic loci rs893818 LOXL1 and rs4886776 LOXL1 were found to be associated with the development of primary open-angle glaucoma in men: the risk factors for POAG are the genotypes GG rs893818 LOXL1 (OR = 1,62; p = 0,025) and GG rs4886776 LOXL1 (OR = 1,59; p = 0,030). Alleles A of these polymorphic loci are of protective importance in the formation of the disease (OR = 0, 59; p = 0,003 for rs893818 and OR = 0,63; p = 0,009 for rs4886776). Conclusion: Polymorphic loci of the LOXL1 gene – rs893818 and rs4886776 are associated with the development of primary open-angle glaucoma in men of the Central Black Earth Region of the Russian Federation.

Keywords: primary open-angle glaucoma, associations, LOXL1, polymorphism.

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Eliseeva NV. A replicative study of the associations of polymorphic loci of the LOXL1 and CDKN2B-AS1 genes with the development of primary open-angle glaucoma in men of the Central Black Earth Region of the Russian Federation. Research Results in Biomedicine. 2020;6(2):198-208. Russian. DOI:
10.18413/2658-6533-2020-6-2-0-4

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Kapetanaris VV, Chan MP, Foster PJ, et al. Global variations and time trends in the prevalence of primary open –angle glaucoma (POAG):systematic review and meta –analysis. British Journal of Ophthalmology. 2016;100(1):86-93. DOI:http://doi:10.1136/bjophthalmol-2015-307223
Barbos YuA, Cherednichenko NL, Karpov SM. Analysis of glaucoma incidence in the Stavropol region. National Journal glaucoma. 2018;17(3):65-75. Russian. DOI: https://doi: org/10.25700/NJG.2018.03.08
Kreft D, Doblhammer G, Guthoff RF, et al. Prevalence, incidence and risk factors of primary open – angle glaucoma – a cohort study based on longitudinal data from a German public health in surname. BMC Public Health. 2019;19:851. DOI: http://doi:10.1186/s12889-019-6935-6
Dzhemileva LU, Zagidullina ASh, Lobov SL, et al. Molecular genetic aspects of primary open-angle glaucoma. Medical Genetics. 2013;12(8):3-14. Russian.
Onischenko AL, Kolbasko AV, Zhilina NM, et al. The incidence of primary glaucoma, its gender characteristics among residents of a large industrial city of Siberia. Ophthalmology in Russia. 2014;11(4):59-67. Russian. DOI: https://doi.org/10.18008/1816-5095-2014-4-59-67
Burdon K, Macgregor S, Hewitt A. et al. Genome-wide association study identifies susceptibility loci for open-angle glaucoma at TMCO1 and CDKN2B-AS1. Nature Genetics. 2011;43(6):574-8. DOI: http://doi.org/10.1038/ng.824
Osman W, Low SK, Takahashi A, et al. A genome-wide association study in the Japanese population confirms 9p21and 14q23 as susceptibility loci for primary open-angle glaucoma. Human Molecular Genetics. 2012;21(12):2836-42. DOI: http://doi.org/10.1093/hmg/dds103
Khor C, Do T, Jia H, et al. Genome-wide association analyses identifies five new susceptibility loci for with primary angle closure glaucoma. Nature Genetics. 2016;48(5):556-62. DOI: http://doi.org/10.1038/ng3540
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. Human Molecular Genetics. 2017;26(2):438-453. DOI: http://doi.org/10.1093/hmg/ddw399
MacGregor S, Ong J, An J, et al. Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma. Nature Genetics. 2018;50(8):1067-1071. DOI: http://doi.org/10.1038/s41588-018-0176-y
Shiga Y, Akiyama M, Nishiguchi KM, et al. Genome-wide association study identifies seven novel susceptibility loci open-angle glaucoma. Human Molecular Genetics. 2018;27(8):1486-1496. DOI: http://doi.org/10.1093/hmg/ddy053
Thorleifsson G, Magnusson KP, Sulem P, et al. Common sequence variants in the LOXL11 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317(5843):1397-400. DOI: http://doi.org/10.1126/science.1146554
Tikunova EV, Churnosov MI. Genetic studies in primary open-angle glaucoma. Vestnik oftal'mologii. 2014;130(5):96-99. Russian.
Kirilenko MYu, Tikunova EB, Sirotina SS, et al. Studying the associations of genetic polymorphisms of growth factors with the development of primary open-angle glaucoma. Vestnik oftal'mologii. 2017;133(3):9-15. Russian. DOI: http://doi.org/10.17116/oftalma 201713339-15
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. International Journal of Ophthalmology. 2017;10(10):1490-1494. DOI: 10.18240/ijo.2017.10.02
Egorov EA, Astakhova YuS, Yericheva VP, editors. National Glaucoma Guide: for practitioners [Internet]. 3rd ed. M.: GEOTAR-Media; 2015 [cited 2020 April 18]. Russian. Available from: https://www.rosmedlib.ru/book/ISBN9785970433140.html
Ponomarenko IV, Reshetnikov EA, Altuchova OB, et al. Association of genetic polymorphisms with age at menarche in Russian women. Gene. 2019;686:228-236. DOI: https://doi.org/10.1016/j.gene.2018.11.042
Nakano М, Ikeda Y, Tokuda Y, et al. Common variants in cdkn2b-asl associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese. PLoS One. 2012;7(3):e33389. DOI: http://doi.org/10.1371/journal.pone.0033389
Ponomarenko IV, Polonikov AV, Churnosov MI. Polymorphic LHCGR gene loci associated with the development of uterine fibroids. . 2018;10:86-91. Russian. DOI: https://dx.doi.org/10.18565/aig.2018.10.86-91
Ponomarenko IV, Reshetnikov EA, Polonikov AV, et al. 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. Obstetrics and Gynecology. 2019;2:98-104. Russian. DOI: https://dx.doi.org/10.18565/aig.2019.2.98-104
Schlotzer-Schrehandf U, Hammer CM, Krysta AW, et al. Molerular pathology of preudoexfoliation syndrome / glaucoma – new insighrs from LOXL1 gene associations. Ophthalmologe. 2012;109(10):944-51. DOI: http://doi:10.1007/s00347-012-25-31-1
Nakano M, Ikeda Y, Tokuda Y, et al. Novel Common variants susceptible haplotype for exfoliation glaucoma specific to Asian population. Scientific Reports. 2014;4:5340. DOI: http://doi.org/10.1038/scep05340
Aung T, Ozaki M, Mizoguchi T, et al. A common variants mapping to CACNA1A is associated with susceptibility to exfoliation syndrome. Nature Genetics. 2015;47(4):387-92. DOI: http://doi.org/10.1038/ng.3226

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