vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-15vavilov-4484Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSОсобенности полиморфизма генов толл-лайк рецепторов (TLR-2, TLR-3, TLR-4 и TLR-6) при открытоугольной глаукомеFeatures of toll-like receptor genes (TLR-2, TLR-3, TLR-4 and TLR-6) polymorphism in open-angle glaucoma patientshttps://orcid.org/0000-0001-5898-950XШевченкоА. В.ShevchenkoA. V.

Новосибирск

Novosibirsk

shalla64@mail.ruhttps://orcid.org/0000-0001-7290-1631ПрокофьевВ. Ф.ProkofievV. F.

Новосибирск

Novosibirsk

https://orcid.org/0000-0001-7385-6270КоненковВ. И.KonenkovV. I.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-7623-3359ЧерныхВ. В.ChernykhV. V.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-7592-8984ТруновА. Н.TrunovA. N.

Новосибирск

Novosibirsk

Научно-исследовательский институт клинической и экспериментальной лимфологии – филиал Федерального исследовательского центра Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияResearch Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationНовосибирский филиал Национального медицинского исследовательского центра «МНТК «Микрохирургия глаза» им. академика С.Н. Федорова Министерства здравоохранения Российской ФедерацииРоссияNovosibirsk Branch of the S.N. Fedorov National Medical Research Center “MNTK “Eye Microsurgery” of the Ministry of Health of the Russian FederationRussian Federation202504032025291128134Copyright © Шевченко А.В., Прокофьев В.Ф., Коненков В.И., Черных В.В., Трунов А.Н., 20252025Шевченко А.В., Прокофьев В.Ф., Коненков В.И., Черных В.В., Трунов А.Н.Shevchenko A.V., Prokofiev V.F., Konenkov V.I., Chernykh V.V., Trunov A.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4484

   Современные исследования показывают, что в патогенезе первичной открытоугольной глаукомы (ПОУГ) важную роль играет врожденный иммунитет. Выявлено повышение содержания толл-лайк рецепторов (TLR) в глаукоматозной сетчатке глаза человека. TLR могут модулировать иммунный ответ при глаукоме, обеспечивают раннее распознавание повреждающих агентов, активацию сигнальных путей и эффекторных механизмов системы неспецифической иммунной защиты, направленных на восстановление гомеостаза. Полиморфизм кодирующих TLR генов влияет на аминокислотную структуру рецепторов, приводя к изменению лигандсвязывающей и корецепторной функции, транспортировку и передачу сигналов.

   Целью работы был анализ ассоциированности полиморфизма генов TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810) с первичной открытоугольной глаукомой у пациентов Западной Сибири.

   Обследовано 99 пациентов (52 мужчины и 47 женщин) с диагнозом первичной открытоугольной глаукомы. Группу сравнения составили 100 человек (81 женщина и 19 мужчин). Полиморфизм генов TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810) анализировали методом РТ-ПЦР с использованием коммерческих тест-систем с интеркалирующим красителем Syber Green (Lytex, Россия). Статистический анализ проводился с использованием программного пакета SPSS 23.0 и Arlequin 3.5.2.2. Показано, что распределение полиморфных маркеров в группе пациентов и в контрольной группе соответствовало равновесию Харди–Вайнберга. Их частоты между двумя анализируемыми группами достоверно не различались. Частота TLR2-753 ArgArg:TLR6-249 ProPro была повышена в группе пациентов с ПОУГ. Выявлено неравновесное сцепление между двумя полиморфными позициям гена TLR4. Кроме того, выявлено нарушение равновесия между парами генов TLR2-TLR6 для группы с глаукомой и контрольной группы. Повышение определенных генотипов в группе пациентов относительно контрольной группы может косвенно свидетельствовать об участии инфекционных факторов в инициации ПОУГ. Однако связь полиморфизма TLR генов, несмотря на доказанную значимость участия их белковых продуктов в патогенезе глаукомы, требует дополнительных исследований с учетом этнических особенностей пациентов и межгенных взаимодействий для лучшего понимания сложных механизмов развития заболевания. Это поможет проводить раннюю диагностику и разрабатывать необходимую терапевтическую стратегию.

   Modern research shows that innate immunity plays an important role in the pathogenesis of primary open-angle glaucoma (POAG). An increase in the content of toll-like receptors (TLR) in the glaucomatous retina of the human eye was revealed. TLRs can modulate the immune response in glaucoma; provide early recognition of damaging agents, activation of signaling pathways and effector mechanisms of the nonspecific immune defense system aimed at restoring homeostasis. The TLR-encoding genes’ polymorphism alters the amino acid structure of the receptors, which leads to changes in their immune functions: expression level, ligand-binding and coreceptor functions, transport and signal transmission.

   The aim was to analyze the association of the TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790, rs4986791) and TLR6 (rs5743810) polymorphisms with primary open-angle glaucoma in patients of Western Siberia.

   Methods

   Methods: 99 patients (52 men and 47 women) with a diagnosis of primary open-angle glaucoma were examined. The comparison group consisted of 100 people (81 women and 19 men). TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790, rs4986791) and TLR6 (rs5743810) polymorphisms were analyzed by RT-PCR using test systems with Syber Green (Lytex, Russia). Statistical analysis was performed using the software package SPSS 23.0 and Arlequin 3.5.2.2.

   Results

   Results: the distribution of genotypes in the patient group and in the control group corresponded to the Hardy–Weinberg equilibrium. The genotype frequencies did not significantly differ between the two analyzed groups. The frequency of TLR2-753 ArgArg:TLR6-249 ProPro was increased in the group of patients with POAG. The linkage disequilibrium between two polymorphic positions of the TLR4 gene was revealed. In addition, the linkage disequilibrium between TLR2-TLR6 gene for the glaucoma group and the control group was revealed.

   Conclusion

   Conclusion: an increase in certain genotypes in the patient group relative to the control group may indirectly indicate the involvement of infectious factors in the initiation of POAG. However, despite the proven importance of the participation of their protein products in the pathogenesis of glaucoma, the relationship of TLR polymorphism requires additional research taking into account the ethnic characteristics of patients and intergenic interactions for a better understanding of the complex mechanisms of disease development. This will help carry out early diagnosis and develop the necessary therapeutic strategy.

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The authors declare that there are no conflicts of interest present.