The severity of endothelial dysfunction, oxidative stress, lipid metabolism disorders, decreased elastic properties and tone of peripheral vessels in patients with different POAG course variants, depending on the polymorphism of the genes of the biological clock

Abstract

The purpose is to find out the relations of the vascular endothelium dysfunction, atherosclerotic damage to the vessels of the upper and lower limbs, the state of the antioxidant and prooxidant systems, and the lipid profile in patients with different POAG course — carriers of biological clock gene polymorphism.Materials and methods. 47 patients with advanced POAG underwent an examination that included visometry, biomicroscopy, ophthalmoscopy, perimetry, tonometry, thermometry, as well as determination of lipid metabolism, indicators of oxidative stress and antioxidant system. All patients were also tested for the degree of endothelial dysfunction by reactive hyperemia method, and the elastic properties and vascular wall tone by the volumetric sphygmomanometry method. POAG progression was determined by static automated perimetry and optical coherence tomography. The hospitalized patients were examined for daily melatonin profile and key biological clock genes typed by real-time polymerase chain reaction. The genetic material was taken by buccal scraping. Polymorphic variants were identified for CLOCK rs1801260 3111T/C and MTNR1B genes. 16 patients (S-POAG — 8, A-POAG — 8) were tested for melatonin taken from saliva samples at different times of the day in laboratory conditions with controlled nutrition and lighting using the DLMO protocol.Results. The predictors of glaucoma progression were found to be pronounced endothelial dysfunction and oxidative stress, which contribute to the acceleration of atherogenesis and a decrease in the elastic properties of the vascular wall of peripheral vessels. Clock 3111t-c circadian gene polymorphism was found to be interrelated with lipid metabolism disorders and increased lipid peroxidation in patients with POAG progression. Carriers of the G allele of the MTNR1B gene tend to have a higher level of triglyceride (TG) which grows in the evening hours if glaucoma is progressing. We showed that the phasal and amplitude characteristics of daily melatonin level, rather than its average level, may affect the state of the vascular wall of peripheral vessels in POAG patients.Conclusion. POAG progression is associated with pronounced oxidative stress, weakened antioxidant protection and dyslipoproteinemia. Differences in the lipid profile (dyslipidemia) and the indicators of oxidative stress and antioxidant protection in patients with stable and progressing glaucoma course are mutually related with Clock 3111t-c gene polymorphism (CG genotype).

Keywords

• endothelial dysfunction
• polymorphism of key genes
• biological rhythms
• melatonin
• primary open-angle glaucoma