Relationship between rs1799983 and rs2070744 polymorphism of the NOS3 gene with primary open-angle glaucoma

Authors

  • O.A. Isaev Dnipro State Medical University, Dnipro, Ukraine; Public Utility “Dnipropetovsk Regional Clinical Ophthalmologic Hospital”, Dnipro, Ukraine

DOI:

https://doi.org/10.22141/2309-8147.10.1.2022.286

Keywords:

primary open-angle glaucoma, endothelial dysfunction, NOS3 gene, rs1799983, rs2070744

Abstract

Background. The development of endothelial dysfunction (EDF) significantly impacts the development of primary open-angle glaucoma (POAG) due to its ability to provoke vasoconstriction and ischemia of the optic nerve, which accele­rates the progression of glaucomatous optic neuropathy. Patients with a hereditary predisposition to the development of EDF due to polymorphism of the endothelial NO-synthase (NOS3) genes may also be prone to the development of POAG. The study was aimed to establish the relationship of the rs1799983 and rs2070744 polymorphisms of the NOS3 gene with primary open-angle glaucoma. Material and methods. The data of 153 patients (153 eyes) with POAG and 47 controls were analyzed. The age of the patients was 65.0 ± 13.1 years; the duration of the disease was 4.9 ± 5.3 years. A real-time polymerase chain reaction was performed in the blood of patients (Gene Amp® PCR System 7500 Amplifier; USA) ­using the TaqMan Mutation Detection Assays Life-Technology test system (USA). Statistica 10 software (StatSoft, Inc., USA) was used for statistical processing of the obtained results. Results. In POAG patients, an increase in the frequency of the minor TT homozygote rs1799983 (2.8 times; PFet = 0.023) and a decrease in the frequency of the minor TT homozygote rs2070744 (1.9 times; PFet = 0.049) were found when compared with the control. The effect of rs1799983 genotypes on the distribution of patients was statistically significant for stages III and IV (p < 0.02), and the effect of rs2070744 genotypes was only for stage IV (p = 0.006). A relationship with POAG of alleles T rs1799983 (p = 0.016) and C rs2070744 (p = 0.025) was established, which, when stratified by stages, remained for III and IV (p < 0.025). Carriers of genotype TT rs1799983, in comparison with carriers of other genotypes, had higher intraocular pressure, worse perimetry results, less RNFL and GCC thickness, and higher Cup/Disk Area Ratio. Carriers of the CC rs2070744 genotype, in comparison with carriers of the TT genotype, had worse results of the perimetric examination and a smaller thickness of RNFL and GCC. Conclusions. The results obtained confirmed the presence of a relationship between the rs1799983 and rs2070744 polymorphisms of the NOS3 gene with POAG in patients of the Ukrainian population. The mechanism of realization of the influence of polymorphisms can be considered a tendency to develop EDF, which can accelerate the progression of glaucomatous optic neuropathy.

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References

Bourne R.R. Vision 2020: where are we? Curr. Opin. Ophthalmol. 2020. 31(2). 81-84. 117. doi: 10.1097/ICU.0000000000000647.

Schuster A.К., Erb C., Hoffmann E.М., Dietlein T., Pfeiffer N. The diagnosis and treatment of glaucoma. Dtsch Arztebl. Int. 2020. 117(13). 225-34. doi: 10.3238/arztebl.2020.0225.

Nesterov A.P. Glaucoma. Moscow: LTD "Medical Information Agency", 2014. 360 р. [in Russian]

Evangelho K., Mogilevskaya M., Losada-Barragan M., Vargas-Sanchez J.K. Pathophysiology of primary open-angle glaucoma from a neuroinflammatory and neurotoxicity perspective: a review of the literature. Int. Ophthalmol. 2019. 39(1). 259-71. doi: 10.1007/s10792-017-0795-9.

Hoguet A. et al. The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma: A Report by the American Academy of Ophthalmology. Ophthalmology. 2019 Apr. 126(4). 611-622. doi: 10.1016/j.ophtha.2018.11.019.

Bracha P., Moore N.А., Ciulla T.А., WuDunn D., Cantor L.B. The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: a review. Surv. Ophthalmol. 2018. 63(3). 281-95. doi: 10.1016/j.survophthal.2017.08.008.

Mudassar I.В. et al. Microvascular endothelial function and primary open angle glaucoma. Ther. Adv. Ophthalmol. 2019. 11. 2515841419868100. doi: 10.1177/2515841419868100.

Liu Y., Allingham R.R. Major review: Molecular genetics of primary open-angle glaucoma. Exp. Eye Res. 2017. 160. 62-84. doi: 10.1016/j.exer.2017.05.002.

Luo Z., Jia A., Lu Z., Muhammad I., Adenrele A., Song Y. Associations of the NOS3 rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis. Postgrad. Med. J. 2019. 95(1125). 361-371. doi: 10.1136/postgradmedj-2019-136396.

Jeoung J.W. et al. The relation between endothelial nitric oxi­de synthase polymorphisms and normal tension glaucoma. J. Glaucoma. 2017. 26(11). 1030-1035. doi: 10.1097/IJG.0000000000000751.

Salari N., Bokaee S., Farshchian N., Mohammadi M., Kazeminia M. The role of polymorphisms rs2070744 and rs1799983 eNOS gene in patients with POAG: a systematic review and meta-analysis. Int. Ophthalmol. 2021 Apr 10. doi: 10.1007/s10792-021-01832-y. Epub ahead of print. PMID: 33837898.

Kondkar A.А. et al. Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort. PLoS ONE. 2020. 15(1). e0227417. doi: 10.1371/journal.pone.0227417.

Magalhães da Silva T. et al. Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population. Gene. 2012. 502(2). 142-6. doi: 10.1016/j.gene.2012.04.047.

Torres L.А., Hatanaka M. Correlating structural and functional damage in glaucoma. J. Glaucoma. 2019. 28(12). 1079-1085. doi: 10.1097/IJG.0000000000001346.

Glaucoma. American Optometric Association. 2020 [Internet]. Available from: https://www.aoa.org/healthy-eyes/eye-and-visionconditions/glaucoma?sso = y.

Kang J.H., Wiggs J.L., Haines J., Abdrabou W., Pasqua­le L.R. Reproductive factors and NOS3 variant interactions in primary open-angle glaucoma. Mol. Vis. 2011. 17. 2544-2551. Epub 2011 Sep 30. PMID: 22025889; PMCID: PMC3198482.

Weiss J. et al. No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients. Mol. Vis. 2012. 18. 2174-2181. Epub 2012 Aug 7. PMID: 22919264; PMCID: PMC3425578.

Cyr A.R., Huckaby L.V., Shiva S.S., Zuckerbraun B.S. Nit­ric oxide and endothelial dysfunction. Crit. Care Clin. 2020. 36(2). 307-321. doi: 10.1016/j.ccc.2019.12.009.

Emam W.А. et al. Endothelial nitric oxide synthase polymorphisms and susceptibility to high-tension primary open-angle glaucoma in an Egyptian cohort. Mol. Vis. 2014. 20. 804-811. PMID: 24940036; PMCID: PMC4057245.

Xiang Y., Dong Y., Li X., Tang X. Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis. J. Ophthalmol. 2016. 2016. 1348347. doi: 10.1155/2016/1348347.

Kang J.Н., Wiggs J.L., Haines J., Abdrabou W., Pasqua­le L.R. Reproductive factors and NOS3 variant interactions in primary open-angle glaucoma. Mol. Vis. 2011. 17. 2544-51. Epub 2011 Sep 30. PMID: 22025889; PMCID: PMC3198482.

Kang J.Н., Wiggs J.L., Rosner B.А., Haines J., Abdrabou W., Pasquale L.R. Endothelial nitric oxide synthase gene variants and primary open-angle glaucoma: interactions with hypertension, alcohol intake, and cigarette smoking. Arch. Ophthalmol. 2011 Jun. 129(6). 773-80. doi: 10.1001/archophthalmol.2011.118.

McMonnies C.W. Glaucoma history and risk factors. J. Optom. 2017. 10(2). 71-8. doi: 10.1016/j.optom.2016.02.003.

Published

2022-05-17

Issue

Section

Clinical Ophthalmology