The severity of essential hypertension in terms of blood pressure values does not depend on NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphisms in the West-Ukrainian population

Objective: to evaluate the association of essential arterial hypertension (EAH) and its severity with genes polymorphism of NOS3 (rs2070744) and GNB3 (rs5443) in West-Ukrainian population. Materials and methods. One-hundred EAH patients (48 – healthy control) participated in the cohort case-control study. Blood pressure (BP), Creatinine, glucose, lipids panel were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFX96™Real-Time PCR). Risk assessed by Relative Risk, Odds Ratio and 95% Confidential intervals. Results. A mutation of the NOS3 gene (786T>C, rs2070744) and the GNB3 gene (825C>T, rs5443) in the homozygous state in the West-Ukrainian population suffers from EAH occurs with a frequency of 16.67% and 8.33%, with no differences with the control subjects (p>0.05). In both groups dominate the T-allele of the NOS3 gene and the C-allele of the GNB3 gene: in patients by 12.5% ​​(c2=4.50; p=0.034) and 41.66% (c2=50.0; p<0.001), in the control – by 25.0% (c2=12.0; p<0.001) and 40.0% (c2=33.33; p<0.001), respectively. The results of the binary logistic regression analysis did not confirm the prediction of the EAH appearance by polymorphic variants of the NOS3 (rs2070744) and GNB3 (rs5443) genes. However, the TT genotype of the GNB3 gene (rs5443) increases unreliably the EAH risk almost twice as likely [OR=2.0; OR 95%CI:0.40-10.82; p>0.05]. Epidemiological analysis did not confirm the association of the NOS3 gene with the EAH severity. But T-allele of the GNB3 gene increases the probability of high normal BP almost 5 times [OR=4.86; OR 95%CI:0.99-24.75; p=0.042]. Conclusions: NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphisms are not associated with blood pressure values and EAH severity as well.

Genetic Predictors of Vascular Regulation of Glaucoma Optic Neuropathy Progression in Patients With Primary Open-Angle Glaucoma

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.

Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes

Aim Activation of the renin-angiotensin-aldosterone system, decreased nitric oxide production, chronic inflammation, and oxidative stress result in subclinical changes in the arterial wall, which favor the development of cardiovascular diseases (CVD). The effect of allelic gene variants that encode the proteins participating in pathogenetic pathways of age-associated diseases with subclinical changes in the arterial wall [increased pulse wave velocity (PWV), increased intima-media thickness, endothelial dysfunction (ED), presence of atherosclerotic plaques (ASP)] are understudied. This study analyzed the relationship between AGT, ACE, NOS3 TNF, MMP9, and CYBA gene polymorphism and the presence of subclinical changes in the arterial wall, including the dependence on risk factors for CVD, in arbitrarily healthy people of various age.Material and methods The relationship of polymorphisms с.521С>Т of AGT gene, Ins>Del of AСE gene, с.894G>T of NOS3 gene, – 238G>A of TNF gene, – 1562С>T of MMP9 gene, and c.214Т>С of CYBA gene with indexes of changes in the arterial wall and risk factors for CVD was studied in 160 arbitrarily healthy people by building models of multiple logistic regression and also by analyzing frequencies of co-emergence of two signs with the Pearson chi-squared test (χ2) and Fisher exact test.Results The DD-genotype of Ins>Del ACE gene polymorphism was correlated with increased PWV (p=0.006; odds ratio (OR) =3.41, 95 % confidence interval (CI): 1.48–8.67) and ED (p=0.014; OR=2.60, 95 % CI: 1.22–5.68). The GG genotype of с.894G>T NOS3 gene polymorphism was correlated with ED (p=0.0087; OR=2.65, 95 % CI: 1.26–5.72); the ТТ-genotype of с.894G>T NOS3 gene polymorphism was correlated with ASP (p=0.033; OR=0.034, 95 % CI: 0.001–0.549).Conclusion Polymorphic variants of AСE and NOS3 genes correlated with ED, increased arterial wall stiffness, and the presence of subclinical changes in the arterial wall.

POLYMORPHISMS OF ENDOTHELIAL DYSFUNCTION GENES NOS3 AND CYBA IN YAKUT POPULATION

Polymorphisms of different genes can predispose people to various diseases. They can influence the body's physiological response to exogenous risk factors. Polymorphisms of the endothelial dysfunction genes NOS3 and CYBA contribute to the development of socially significant diseases, such as acute coronary syndrome, stroke, as well as diseases accompanied by fibrotic changes (cirrhosis of the liver, pulmonary fibrosis, etc.). Therefore, the study of these genes in the Yakut population seems relevant. The present study involved 124 healthy volunteers, their ethnicity is Yakuts (including Yakuts in the third generation, living in the Republic of Sakha (Yakutia)). Genetic analysis of polymorphisms was performed by the method of polymerase chain reaction of restriction fragment length polymorphisms (PCR-RFLP). The study found that healthy Yakuts have GG homozygote of rs1799983 of the NOS3 gene in 83.87%, GT - 15.32%, TT - 0.81%. The frequency of the G allele was 91.53%, the T allele - 8.47%. The study found that healthy Yakuts have CC homozygote of rs4673 of the CYBA gene in 75.0%, CT - 21.77%, TT - 3.23%. The frequency of C allele was 91.44%, T - 8.56%. These results are consistent with the literature data. Thus, the research of the polymorphism rs1799983 of the NOS3 gene and rs4673 of the CYBA gene in various ethnic groups could have encouraging prospects in the personalized medicine for predicting pathological conditions associated with endothelial dysfunction: liver fibrosis, cardiovascular diseases, obstetric and gynecological pathologies, dysfunctions of various organs and systems.

The T786C polymorphism of NOS3 gene effect on the level of nitric oxide metabolites among patients with non-valvular paroxysmal atrial fibrillation

The objective of the research - to determine the the T786C polymorphism of nos3 gene effect on the level of nitric oxide metabolites among patients with non-valvular paroxysmal atrial fibrillation.Material and methods. To achieve this goal, a prospective study was conducted on the basis of the communal uncommercial company “City Hospital № 10” of Zaporizhzhia City Council. The sample of patients was conducted in the period from 2014 to 2019. The results of the study are based on data from a comprehensive examination and dynamic monitoring of 176 patients with paroxysmal atrial fibrillation on the background of coronary heart disease combined with hypertension, of which 98 were from the city of Zaporizhzhia and 78 were from rural areas. Almost healthy 31 volunteers were examined on an outpatient basis.Results. Plasma NO2 levels in both groups area urban and rural patients - 7.02 [5.74 ; 8.14] mmol/L and 6.77 [5.47 ; 7.98] mmol/l, respectively, were significantly lower compared to 8.46 [7.45 ; 9.45] mmol/L in the healthy group (p<0.05). Significantly, the lowest level of NO3 was in the group of patients from the city of 10.36 [8.14 ; 13.32] mmol/L, in vs. to the value of 11.69 [10.36; 15.33] mmol/L in the group of patients from rural areas and against 13.36 [11.85 ; 15.35] mmol/L in the group of healthy individuals, (p<0.05). The highest value of NO2+NO3 was in the group of healthy people - 21.56 [20.38 ; 24.53] mmol/L, against the level of 18.02 [15.83 ; 21.78] mmol/L in the group of patients from rural areas and - 17.60 [14.80 ; 20.35] mmol/L in the group from urban area (p < 0.05). The median NO2 level in the subgroup of homozygotes for the T allele was 7.86 [6.66; 8.88] mmol/L and was significantly higher than in the subgroup of heterozygotes TC - 6.66 [5.18; 7.98] mmol/L – and the subgroup of homozygotes for the C - 5.81 [5.07; 6.72] mmol/l (p<0.05). The highest value of NO2+NO3 was in the homozygote subgroup for the T - 20.35 [17.07 ; 25.16] mmol/l, both against the level of 17.52 [15.37 ; 20.72] mmol/L of the TC heterozygote subgroup, and against 16.41 [14.48; 17.93] mmol/L of the homozygote subgroup for the C allele (p<0.05). However, there was no significant difference between the heterozygote and homozygote subgroups for the C allele (p>0.05). Conclusions. Decreased nitric oxide metabolites occur among patients with non-valvular paroxysmal atrial fibrillation compared with the healthy group. The level of nitrate-ions in the group of patients from the city was significantly lower than in the group of patients from the rural areas. The level of nitrite-ions was lower among patients with the C allele of the T786C polymorphism of the 3 type of nitric oxide synthase gene, whereas the value of nitrate-ions did not depend on this polymorphism.

The impact of NOS3 gene polymorphism on papillary thyroid cancer susceptibility in patients undergoing radioiodine therapy

Thyroid cancer is the most common endocrine cancer in the world. Noting that the NOS3 gene polymorphism interferes with nitric oxide production, this study aims to identify and analyze the NOS3 gene polymorphism in the intron 4 region in patients with papillary thyroid cancer. A case-control study was conducted with 31 papillary thyroid cancer patients of both genders who underwent thyroidectomy and treatment with sodium iodide radiopharmaceutical (131I) compared with 81 control patients. Through papillary thyroid cancer, the results were observed, compiled, and analyzed using SPSS version 25.0. The significance level of 5% was adopted. Genotypic frequencies of healthy subjects were in the Hardy-Weinberg equilibrium ( P = 0.503). There was a significant genotypic difference between papillary thyroid cancer and healthy individuals ( P <0.001). The BB genotype conferred a protective factor for papillary thyroid cancer ( P <0.001, odds ratio (OR) 0.16; 95% confidence interval (CI) 0.06, 0.42), while the presence of the A allele appears to be a risk factor for papillary thyroid cancer ( P <0.001, OR 3.54; 95% CI 1.86, 6.73). The intron 4 polymorphism of the NOS3 gene was associated with susceptibility to papillary thyroid cancer. Thus, future research into the effects of this polymorphism is essential.