Abstract
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.
Highlights
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
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
The clock rs1801260 and MTNR1B rs10830963 gene polymorphism was found to be related to disturbances in melatonin production and sleep phase
Summary
В ходе исследования установлено, что фактором, влияющим на ритм продукции мелатонина слюны при ПОУГ, являются полиморфизмы генов MTNR1B, а также CLOCK rs1801260 Т/С (3111T > C, rs1801260). Сочетание генотипов TT полиморфного маркера rs1801260 гена CLOCK rs1801260 и CG полиморфного маркера rs10830963 гена рецептора мелатонина II типа MTNR1В, вероятно, может взаимно потенцировать фазовый сдвиг синтеза мелатонина на более позднее время у пациентов с ПОУГ. У лиц с генотипом CLOCK rs1801260 TT наблюдается более низкий уровень мелатонина в ночное время, что, однако, наблюдается только в сочетании с носительством G-аллеля гена MTNR1B Сдвиг фазы сна на более поздние часы у носителей G-аллеля гена мелатонинового рецептора MTNR1B rs10830963 свойствен пациентам с прогрессирующей глаукомой (A-POAG) Сдвиг фазы сна на более поздние часы у носителей G-аллеля гена мелатонинового рецептора MTNR1B rs10830963 свойствен пациентам с прогрессирующей глаукомой (A-POAG) (рис. 5)
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