Журнал микробиологии, эпидемиологии и иммунобиологии. 2022; 99: 54-62
Роль полиморфизма гена eNOS в иммунопатогенезе первичной открытоугольной глаукомы
https://doi.org/10.36233/0372-9311-221Аннотация
Введение. Патологии органа зрения (кератиты, глаукома и др.) занимают ведущее место среди причин снижения зрения и слепоты. По данным литературы, иммунопатогенез бактериальных кератитов связан с активацией макрофагов и кислородным взрывом. Не до конца понятна роль этих механизмов в патогенезе первичной открытоугольной глаукомы. Есть единичные работы, в которых связывают развитие этой патологии с оксидом азота NO, который продуцируется эндотелиальной NO-синтазой (eNOS). Однако, несмотря на многочисленные исследования, роль иммуногенетических в патогенезе глаукомы остаются недостаточно исследованными.
Цель работы — изучение роли полиморфных маркеров T786C, C774T, Glu298Asp гена eNOS при развитии ПОУГ у жителей Пермского края.
Материалы и методы. В качестве материала была использована периферическая кровь 93 пациентов с ПОУГ и 96 пациентов с катарактой. Сначала выделяли ДНК, затем проводили полимеразную цепную реакцию в режиме реального времени. Частоту встречаемости аллелей и генотипов в исследуемых группах рассчитывали при помощи критерия χ2 и точного критерия Фишера. Статистически значимыми были приняты результаты с p < 0,05. Для количественной оценки связи между возникновением ПОУГ у пациентов и носительством неблагоприятного полиморфного маркера были рассчитаны отношение шансов и 95% доверительный интервал.
Результаты. Среди маркеров С774Т и Glu298Asp не выявлено достоверных различий в распределении генотипов и аллелей гена eNOS. Установлены повышение частоты встречаемости гомозиготного генотипа ТТ; снижение встречаемости аллеля С по полиморфному локусу T786C гена eNOS у пациентов с ПОУГ.
Выводы. Полиморфные маркеры гена eNOS могут рассматриваться как факторы, влияющие на вероятность возникновения ПОУГ.
Список литературы
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19. 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. https://doi.org/10.1155/2016/1348347
20. Kondkar A.A., Azad T.A., Almobarak F.A., Abu-Amero K.K., Al-Obeidan S.A. Polymorphism rs7961953 in TMTC2 gene is not associated with primary open-angle glaucoma in a Saudi cohort. Ophthalmic Genet. 2019; 40(1): 74–6. https://doi.org/10.1080/13816810.2019.1576210
21. Kondkar A.A., Sultan T, Almobarak F.A., Kalantan H., Abu-Amero K.K., Al-Obeidan S.A. Plexin domain containing 2 (PLXDC2) gene polymorphism rs7081455 may not influence POAG risk in a Saudi cohort. BMC Res. Notes. 2018; 11(1): 733. https://doi.org/10.1186/s13104-018-3848-x
22. Kondkar A.A., Azad T.A., Almobarak F.A., Bahabri I.M., Kalantan H., Abu-Amero K.K., et al. Lack of association between variant rs7916697 in ATOH7 and primary open angle glaucoma in a Saudi cohort. Genet. Res. Int. 2018; 2018: 2148056. https://doi.org/10.1155/2018/2148056
23. Kondkar A.A., Azad T.A., Sultan T., Al-Mobarak F.A., Kalantan H., Al-Obeidan S.A. Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case-control study. BMC Res. Notes. 2019; 12(1): 453. https://doi.org/10.1186/s13104-019-4491-x
24. Lip P.L., Felmeden D.C., Blann A.D., et al. Plasma vascular endothelial growth factor, soluble VEGF receptor FLT-1, and von Willebrand factor in glaucoma. Br J Ophthalmol. 2002; 86(11): 1299–302. https://doi.org/10.1136/bjo.86.11.1299
Journal of microbiology, epidemiology and immunobiology. 2022; 99: 54-62
The role of eNOS gene polymorphisms in immunopathogenesis of primary open-angle glaucoma
https://doi.org/10.36233/0372-9311-221Abstract
Introduction. Pathologies of the visual organ (keratitis, glaucoma, etc.) occupy a leading place among the causes of vision loss and blindness. According to the literature, the immunopathogenesis of bacterial keratitis is associated with the activation of macrophages and oxygen explosion. The role of these mechanisms in the pathogenesis of primary open-angle glaucoma is not fully understood. There are isolated studies in which the development of this pathology is associated with nitric oxide NO, which is produced by endothelial NO synthase (nos). However, despite numerous studies, the role of immunogenetics in the pathogenesis of glaucoma remains insufficiently researched.
The aim of the study is to explore the association of T786C, C774T, Glu298Asp polymorphic markers of the eNOS gene with development of POAG in residents of the Perm Territory.
Materials and methods. The study was performed using peripheral blood collected from 93 patients with POAG and 96 patients with cataracts. The real-time polymerase chain reaction was performed after the DNA extraction. The frequencies of alleles and genotypes in the study groups were measured using the chi-square (χ2 ) test and Fisher’s exact test. Results with p < 0.05 were seen as statistically significant. The calculated odds ratio and the 95% confidence interval were used to quantify the association between POAG development in patients and the existence of an unfavorable polymorphic marker.
Results. The C774T and Glu298Asp markers did not show any significant differences in the distribution of genotypes and alleles of the eNOS gene. Higher frequencies of the homozygous TT genotype; and lower frequencies of the C allele of T786C polymorphic locus of eNOS gene were detected in patients with POAG.
Conclusion. Polymorphic markers of the eNOS gene can be seen as factors associated with the risk of POAG.
References
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12. 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. https://doi.org/10.1007/s10792-017-0795-9
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14. Ozkan J.S., Majzoub M.E., Coroneo M.S., Thomas T., Willcox M. Comparative analysis of ocular surface tissue microbiome in human, mouse, rabbit, and guinea pig. Exp. Eye Res. 2021; 207: 108609. https://doi.org/10.1016/j.exer.2021.10860
15. Weinreb R.N., Khaw P.T. Primary open-angle glaucoma. Lancet. 2004; 363(9422): 1711–20. https://doi.org/10.1016/S0140-6736(04)16257-0
16. Kondkar A.A., Azad T.A., Sultan T., Osman E.A., Almobarak F.A., Al-Obeidan S.A. Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort. PLoS One. 2020; 15(1): e0227417. https://doi.org/10.1371/journal.pone.0227417
17. Wink D.A., Miranda K.M., Espey M.G., luta R.M., Hewett S.J., Colton C., et al. Mechanisms of the antioxidant effects of nitric oxide. Antioxid. Redox Signal. 2001; 3(2): 203–13. https://doi.org/10.1089/152308601300185179
18. Ster A.M., Popp R.A., Petrisor F.M., Stan C., Pop V.I. The role of oxidative stress and vascular insufficiency in primary open angle glaucoma. Clujul Med. 2014; 87(3): 143–6. https://doi.org/10.15386/cjmed-295
19. 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. https://doi.org/10.1155/2016/1348347
20. Kondkar A.A., Azad T.A., Almobarak F.A., Abu-Amero K.K., Al-Obeidan S.A. Polymorphism rs7961953 in TMTC2 gene is not associated with primary open-angle glaucoma in a Saudi cohort. Ophthalmic Genet. 2019; 40(1): 74–6. https://doi.org/10.1080/13816810.2019.1576210
21. Kondkar A.A., Sultan T, Almobarak F.A., Kalantan H., Abu-Amero K.K., Al-Obeidan S.A. Plexin domain containing 2 (PLXDC2) gene polymorphism rs7081455 may not influence POAG risk in a Saudi cohort. BMC Res. Notes. 2018; 11(1): 733. https://doi.org/10.1186/s13104-018-3848-x
22. Kondkar A.A., Azad T.A., Almobarak F.A., Bahabri I.M., Kalantan H., Abu-Amero K.K., et al. Lack of association between variant rs7916697 in ATOH7 and primary open angle glaucoma in a Saudi cohort. Genet. Res. Int. 2018; 2018: 2148056. https://doi.org/10.1155/2018/2148056
23. Kondkar A.A., Azad T.A., Sultan T., Al-Mobarak F.A., Kalantan H., Al-Obeidan S.A. Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case-control study. BMC Res. Notes. 2019; 12(1): 453. https://doi.org/10.1186/s13104-019-4491-x
24. Lip P.L., Felmeden D.C., Blann A.D., et al. Plasma vascular endothelial growth factor, soluble VEGF receptor FLT-1, and von Willebrand factor in glaucoma. Br J Ophthalmol. 2002; 86(11): 1299–302. https://doi.org/10.1136/bjo.86.11.1299
