helmholtzeyeinstituteРоссийский офтальмологический журналRussian Ophthalmological Journal2072-00762587-5760Real time Publishers10.21516/2072-0076-2021-14-4-38-45helmholtzeyeinstitute-780Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESИсследование связи полиморфизма и суточной динамики экспрессии ключевых генов биологических часов с риском прогрессирования первичной открытоугольной глаукомыThe connection of polymorphism and diurnal changes of the biological clock gene expression with the risk of progression of primary open-angle glaucomaВласоваА. С.VlasovaA. S.

Анастасия Сергеевна Власова — аспирант кафедры офтальмологии

ул. Прокопия Артамонова, д. 5/11, Тюмень, 625051

Anastasia S. Vlasova — Ph Dstudent, ophthalmology department

ProkopiyaArtamonova str., 5/11, Tyumen, 625051

okula-83@mail.ruПетровС. А.PetrovS. A.

Сергей Анатольевич Петров — д-р мед. наук, профессор, руководитель отдела биоресурсов криосферы

ул. Прокопия Артамонова, д. 5/11, Тюмень, 625051

Sergey A. Petrov — Dr. of Med. Sci., professor, head of the department of bioresources of the cryosphere

ProkopiyaArtamonova str., 5/11, Tyumen, 625051

МалишевскаяТ. Н.MalishevskayaT. N.

Татьяна Николаевна Малишевская — д-р мед. наук, руководитель отделения аналитической работы

ул. Садовая-Черногрязская, д. 14/19, Москва, 105062

Tatyana N. Malishevskaya — Dr. of Med. Sci., head of the department of analytical work

14/19, Sadovaya-Chernogryazskaya str., Moscow, 105062

ГубинД. Г.GubinD. G.

Денис Геннадьевич Губин — д-р мед. наук, профессор, заведующий кафедрой биологии

ул. Одесская, д. 54, Тюмень, 625150

Denis G. Gubin — Dr. of Med. Sci., professor, head of the department of biology

54, Odesskaya str., Tyumen, 625150

КоломейчукС. Н.KolomeychukS. N.

Сергей Николаевич Коломейчук — канд. биол. наук, заведующий лабораторией генетики, протеомики и метаболомики1, старший научный сотрудник лаборатории генетики

ул. Пушкинская, д. 11, Петрозаводск, 185910

Sergey N. Kolomeychuk — Cand. of Biol. Sci., head of the laboratory of genetics, proteomics and metabolomics1, senior researcher at the laboratory of genetics

11, Pushkinskaya str., Petrozavodsk, 185910

АНЧОО ДПО «Западно-Сибирский институт последипломного медицинского образования»РоссияWest Siberian Institute of Postgraduate Medical EducationRussian FederationФГБУ «НМИЦ глазных болезней им. Гельмгольца» Минздрава РоссииРоссияHelmholtz National Medical Research Center of Eye DiseasesRussian FederationФГБОУ ВО «Тюменский государственный медицинский университет»РоссияTyumen State Medical UniversityRussian FederationФИЦ «Карельский научный центр РАН»РоссияKarelian Scientific Center of the Russian Academy of SciencesRussian Federation2021301220211443845Copyright © Власова А.С., Петров С.А., Малишевская Т.Н., Губин Д.Г., Коломейчук С.Н., 20222022Власова А.С., Петров С.А., Малишевская Т.Н., Губин Д.Г., Коломейчук С.Н.Vlasova A.S., Petrov S.A., Malishevskaya T.N., Gubin D.G., Kolomeychuk S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://roj.igb.ru/jour/article/view/780

Цель работы — изучить взаимосвязь генетических факторов (полиморфизма и экспрессии ключевых генов биологических часов (КГБЧ), подконтрольных КГБЧ, мелатониновых рецепторов) и суточной динамики мелатонина у пациентов со стабильной и прогрессирующей первичной открытоугольной глаукомой (ПОУГ). Материал и методы. Обследовано 115 пациентов в возрасте 53–86 лет (в среднем 68,8 ± 7,9 года) со стабильной и прогрессирующей глаукомой. Всем пациентам проведено первичное офтальмологическое обследование, исследование суточного профиля температуры тела, внутриглазного давления (ВГД), мелатонина (по протоколу DLMO), а также типирование КГБЧ методом полимеразной цепной реакции в реальном времени. Изучался сдвиг фазы сна на более поздние часы у носителей G-аллеля гена мелатонинового рецептора при прогрессировании глаукомы.Результаты. В ходе изучения клинико-генотипических особенностей течения ПОУГ обнаружены фазовые смещения циркадианных ритмов температуры тела, ВГД, уровня мелатонина слюны и фазы сна, способствующие прогрессированию глаукомной нейрооптикопатии. Отдельным частым проявлениям десинхроноза способствуют определенные полиморфные варианты генов. Выявлена взаимосвязь полиморфизма генов CLOCK rs1801260 и MTNR1B rs10830963 с нарушениями продукции мелатонина и фазой сна. Заключение. Комплексными проявлениями циркадной десинхронизации, сопровождающими прогрессирующее течение глаукомы, являются поздняя фаза ритмов и снижение продолжительности сна, температуры тела, мелатонина слюны и ВГД, внутренняя десинхронизация между ВГД и температурой тела, ВГД и сном, вечерняя дислипидемия. Выявленные закономерности открывают перспективы будущих исследований взаимосвязи полиморфизма и суточной динамики экспрессии ключевых генов биологических часов с риском прогрессирования ПОУГ. 

The purpose of this work is to study the connection betweengenetic factors (polymorphism and expression of key genes of the biological clock (KGBC), key genes controlled by KGBC, melatonin receptors) and the diurnal oscillation of melatonin in patients with stable and progressing primary open-angle glaucoma. Materials and methods. The study involved 115 patients aged 53–86 (averagely, 68.8 ± 7.9 years) with stable and progressive glaucoma. All patients underwent primary ophthalmological examination, tested for diurnal body temperature profile, intraocular pressure (IOP), melatonin (by the DLMO protocol) and were typed for key genes of the biological clock using the real-time polymerase chain reaction. We studied the sleep phase shift to later hours in carriers of the G-allele of the melatonin receptor gene during the progression of glaucoma. Results. The study of the clinical and genotypic features of the POAG course revealed phasal shifts of the circadian rhythms of body temperature, IOP, salivary melatonin levels and sleep phases which contributed to the progression of glaucomatous optic neuropathy. Certain polymorphic variants of genes contribute to individual frequent manifestations of desynchronosis. The clock rs1801260 and MTNR1B rs10830963 gene polymorphism was found to be related to disturbances in melatonin production and sleep phase. Conclusion. Complex manifestations of circadian desynchronization accompanying the progressive course of glaucoma are the late phase of rhythms and a decrease in sleep duration, body temperature, salivary melatonin and IOP, internal desynchronization between IOP and body temperature, IOP and sleep, evening dyslipidemia. The revealed patterns open up prospects for future studies of the relationship between polymorphism and daily changes of the expression of key genes in the biological clock with the risk of progression of primary open angle glaucoma.

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