The WHO Global vision detection program and preventing blindness "VISION 2020: the right to Sight" has shown the need to identify the genetic predisposition to glaucoma. It provides new opportunities for diagnosis, early prevention and treatment. The aim of this study was to determine the effect of the rs1799983 polymorphism (G894T, Glu298Asp) of the NOS3 gene on the development of primary open-angle glaucoma (POAG) in patients from the Ukrainian population. The study involved data from 153 patients (153 eyes) with POAG and 47 controls. The age of patients was 65.0±13.1 years. The duration of the disease was 4.9±5.3 years. The real-time polymerase chain reaction (Gene Amp® PCR system 7500 amplifier; USA) was performed in the patients “blood using the TaqMan Mutation Detection Assays Life-Technology test system (USA). The Statistica 10 program (StatSoft, Inc.) was used for statistical processing of the obtained results, USA). The significant increase in the frequency of the minor genotype TA and the T allele was found in POAG compared to the controls. The distribution of genotypes was not associated with the disease (p=0.051). While the effect of alleles was significant: for the T allele, OR=1.806; 95% VI 1.11-2.93 (p=0.016). It was preserved when it was stratified by gender for women (OR=2.00; OR 1.01-3.95; p=0.043). According to the presence of the risk TT genotype rs1799983, POAG developed at the younger age (p<0.001), such patients had significantly higher intra-abdominal pressure, worse perimetry indicators (MD and PSD), lower thickness of nerve fiber layers (RNFL) and ganglion cell complex (GCC), a larger ratio of excavation area to the area of the optic disc (Cup/Disk Area Ratio). The Association of the RS1799983 polymorphism of the NOS3 gene with PVKG was also confirmed in other populations, and the aggravating effect of the minor TT genotype on the phenotype of patients was shown.
Glaucoma is regarded as a heterogeneous group of diseases with a specific change in biomechanics of the anterior and posterior chambers of the eye, resulting in the increased production and decreased outflow of the aqueous humor. Progressive degeneration of retinal ganglion cells, microglia, astrocytes, Mueller cells leads to chronic damage, thinning of the neuroretinal layer and narrowing of visual field. In this study we investigated primary open-angle glaucoma (POAG). According to many American Optometric Association studies, POAG is the most common type of glaucoma (accounting for up to 72–96 % of cases) characterized by asymptomatic course with gradual decrease in peripheral vision. The reason for this abnormal condition is the optic nerve damage, inefficiency of eye drainage system with fluid accumulation and increased intraocular pressure. Investigation of POAG occurrence and progression becomes more and more relevant each year. Epidemiological studies for the past 50 years showed progressive increase in the incidence of glaucoma. In 5 % of cases, glaucoma is a monogenic disease with Mendelian inheritance. A significant proportion of cases POAG are genetically determined and have a clear hereditary predisposition, which according to various estimates determines from 20 to 60 %. NOS3 gene polymorphism is of considerable scientific interest due to its influence on the development of endothelial dysfunction. Of great scientific interest is determination of the relationship between the rs1799983 and rs2070744 polymorphisms with the development and progression of POAG. Literature review was performed in following database of scientific literature: Web of Science, Google Scholar, PubMed, Scopus etc. Keywords: prevalence of glaucoma, glaucoma epidemiology, gene polymorphism, NOS3 gene, endothelial dysfunction.
Relevance – it is promising to develop a system for the diagnosis and prevention of primary open-angle glaucoma (POAG), which would be based on the determination of constitutive propensity factors and would be able to predict the onset and progression of the disease. The aim of the study was to develop a model for predicting the rate of progression of primary open-angle glaucoma depending on gender and endothelial NO-synthase (NOS3) gene polymorphism. There were genotyped 153 patients with POAG aged 36-84 years. Genotypes rs1799983 and rs207074 were determined in the blood of patients by real-time polymerase chain reaction (amplifier Gene Amp® PCR System 7500; USA) using the TaqMan Mutation Detection Assays Life-Technology test system (USA). For mathematical processing of the obtained results, the Statistica 10 program (StatSoft, Inc., USA) was used. The rate of progression of POAG was higher in the presence of risk alleles in the haplotype of the NOS3 gene polymorphisms: T rs1799983 and C rs2070744 (haplotypes TT-CC, GT-CC and GT-CT), which, when distributed by gender, was more pronounced in women than in men of each of the possible haplotypes. The maximum difference was noted for carriers of the TT-SS haplotype, in whom the rate of progression of POAG in women exceeded that in men by 1.4 times (p<0.001). A regression model was built with satisfactory prediction indicators (multiple correlation coefficient R=0.963; coefficient of determination R2=0.928; p<0.001). The probable “hereditary” age of patients in which one or another stage of POAG should be expected is calculated. Gender and haplotypes rs1799983 and rs2070744 of the NOS3 gene were shown to be associated with the onset and rate of progression of POAG, which was implemented in the prognostic model of the disease. Separately for men and women, carriers of different haplotypes, the rate of progression and the possible age of POAG development by stages were calculated.
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