Risks’ Stratification of Metabolic Disorders and Arterial Hypertension Depending on the NOS3 (RS2070744) and GNB3 (RS5443) Genes’ Allelic State


Andriy Sydorchuk


Early diagnosis of essential arterial hypertension (EAH), the search for risk factors for its occurrence and severity, which determine the metabolome and epigenetic structures activity, is an urgent task of modern medicine.

The objective: to assess the risks of metabolic disorders and the EAH occurrence, depending on the NOS3 (rs2070744) and GNB3 (rs5443) genes’ allelic state.

Materials and methods. 100 patients with EAH and 48 practically healthy (control group) were enrolled in the study. All participant underwent clinical and laboratory examinations. Metabolic changes were examined by blood glucose, total cholesterol (TC), triacylglycerol (TG), high and low density lipoprotein cholesterol (HDL-C, LDL-C), Atherogenicity index (AI). The NOS3 (rs2070744) and GNB3 (rs5443) genes were studied by real-time PCR. Risks, prognoses were determined by the clinical epidemiology method.

Results. The risk of metabolic disorders (dyslipidemia and hyperglycemia) in EAH patients does not depend on NOS3 gene polymorphism (rs2070744). However, the mutational T-allele of the GNB3 gene (825C>T) presence in the patients’ genotype increases the risk of hyperlipidemia due to atherogenic LDL-C 8.5 times [OR=8.45; OR 95%CI:0.99–72.70; p=0.05], with the CC-genotype protective role [OR=0.12; OR 95%CI:0.01–1.0; p=0.048].

The overall risk of EAH in the examined population increases with fasting hyperglycemia 9 times [OR 95%CI:2.86–27.08; p<0.001], with hypertriglyceridemia (>1.70 mmol/l) – 3 times [OR 95%CI:1.23–5.56; p=0.009] and with a decrease in HDL-C (<1.2 mmol/l) – more than 3.5 times [OR 95%CI:1.46–8.71; p=0.003], respectively.

Conclusion. The risk of metabolic disorders increases in EAH patients with the T-allele of the GNB3 gene (825C>T) 8.5 times with the lowest probability of such changes in the CC-genotype carriers [OR=0.12; p=0.048].


How to Cite
Sydorchuk, A. (2022). Risks’ Stratification of Metabolic Disorders and Arterial Hypertension Depending on the NOS3 (RS2070744) and GNB3 (RS5443) Genes’ Allelic State. Family Medicine, (1-2), 31–35. https://doi.org/10.30841/2307-5112.1-2.2022.260501
For practicing physicians
Author Biography

Andriy Sydorchuk, Sumy State University

Andriy R. Sydorchuk,

Medical Institute


World Health Organization. More than 700 million people with untreated hypertension [Internet]. Geneva: WHO; 2021. Available from: https://www.who.int/news/item/25-08-2021-morethan-700-million-people-with-untreated-hypertension.

Nguyen Tu N, Chow Clara K. Global and national high blood pressure burden and control. Lancet. 2021;398(10304):932–3. doi: 10.1016/S0140-6736(21)01688-3.

Zhou B, Carrillo-Larco RM, Danaei G, Riley LM, NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398(10304):957–80. doi: 10.1016/S0140-6736(21)01330-1.

Tegegne BS, Man T, Van Roon AM, Asefa NG, Riese H, Nolte I, et al. Heritability and the Genetic Correlation of Heart Rate Variability and Blood Pressure in >29 000 Families: The Lifelines Cohort Study. Hyperten. 2020;76(4):1256–62. doi: 10.1161/HYPERTENSIONAHA.120.15227.

Sydorchuk LP. Farmakohenetyka arterialnoyi hipertenziyi. Chernivtsi: Vyd-vo BDMU; 2011. 532 p.

Williams B, Mancia G, Spiering W, Agabiti RE, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104. doi: 10.1093/eurheartj/ehy339.

Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227–37. doi: 10.1093/eurheartj/ehab484.

Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hyperten. 2020;75(6):1334–57. doi: 10.1161/HYPERTENSIONAHA.120.15026.

Repchuk Y, Sydorchuk L, Fedoniuk L, Nebesna Z, Vasiuk V, Sydorchuk A, et al. Association of Lipids’ Metabolism with Vitamin D Receptor (rs10735810, rs222857) and Angiotensinogen (rs699) Genes Polymorphism in Essential Hypertensive Patients. Open Access Maced J Med Sci. 2021;9(A):1052–6.

Sydorchuk L, Dzhuryak V, Sydorchuk A, Levytska S, Petrynych V, Knut R, et al. The cytochrome 11B2 aldosterone synthase gene rs1799998 single nucleotide polymorphism determines elevated aldosterone, higher blood pressure, and reduced glomerular filtration, especially in diabetic female patients. Endocrin Regulations. 2020;54(3):217–26. doi:10.2478/enr-2020-0024.

Repchuk Y, Sydorchuk LP, Sydorchuk AR, Fedonyuk LY, Kamyshnyi O, Korovenkova O, et al. Blood pressure, obesity and di-abetes mellitus linkage with an-giotensinogen gene (AGT 704T>C/rs699) polymorphism in hypertensive patients. Bratislava Med J. 2021;122(10):715–20. doi: 10.4149/BLL_2021_114.

Semianiv M, Sydorchuk L, Fedonyuk L, Nebesna Z, Kamyshnyi O, Sydorchuk A, et al. Metabolic and Hormonal Prognostic Markers of Essential Arterial Hypertension Considering the Genes Polymorphism AGTR1 (rs5186) and VDR (rs2228570). Roman J Diabetes Nutr Metabol Dis. 2021;28(3):284–91.

Sydorchuk A, Sydorchuk L. 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. J Educ Health Sport. 2021;11(10):332–41.

Dzhuryak V, Sydorchuk L, Sydorchuk A, Kamyshnyi O, Kshanovska A, Levytska S, et al. The cytochrome 11B2 aldosterone synthase gene CYP11B2 (RS1799998) polymorphism associates with chronic kidney disease in hypertensive patients. Biointerface Res Appl Chem. 2020;10(3):5406–11. doi: 10.33263/BRIAC103.406411.

Sydorchuk LP, Dzhuryak VS, Sydorchuk AR, Levytska SA, Knut RP, Sokolenko MO, et al. Association of lipids' metabolism disorders with aldosterone synthase CYP11B2 (-344C/T) gene polymorphism in hypertensive patients depending on glomerular filtration rate. Pharmacol Online. 2020;2:230–42.

Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111–88. doi: 10.1093/eurheartj/ehz455.

Hsiao TJ, Hwang Y, Liu CH, Chang HM, Lin E. Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population. Genes Nutr. 2013;8:37–144. doi: 10.1007/s12263-012-0304-8.

Li HL, Zhang YJ, Chen XP, Luo JQ, Liu SY, Zhang ZL. Association between GNB3 c.825C > T polymorphism and the risk of overweight and obesity: A meta-analysis. Meta Gen. 2016;9:18–25. doi: 10.1016/j.mgene.2016.03.002.

Faramarziyan N, Rahmati M, Mirnasouri R, Bahrami M. The Association between GNB3 Gene Polymorphism and Obesity: A Systematic Review and Meta-Analysis. IJDO. 2017;9(1 and 2):69–81.

Fattakhov N, Smirnova L, Atochin D, Parshukova D, Skuratovskaia D, Painter Q, et al. Haplotype analysis of endothelial nitric oxide synthase (NOS3) genetic variants and metabolic syndrome in healthy subjects and schizophrenia patients. Int J Obes (Lond). 2018;42(12):2036–46. doi: 10.1038/s41366-018-0124-z.

Misiak B, Krolik M, Kukowka A, Lewera A, Leszczynski P, Stankiewicz-Olczyk J, et al. The Role of −786T/C Polymorphism in the Endothelial Nitric Oxide Synthase Gene in Males with Clinical and Biochemical Features of the Metabolic Syndrome. Int J Endocrinol. 2011;2011:Article ID 458750. doi: 10.1155/2011/458750.

Gaunt TR, Smith GD. eNOS and coronary artery disease: Publication bias and the eclipse of hypothesis-driven meta-analysis in genetic association studies. Gene 2015;556(2):257–8. doi: 10.1016/j.gene.2014.11.052.

Pawlik A, Błaszczyk H, Rać M, Maciejewska-Skrendo A, Safranow K, Dziedziejko V. NOS3 Gene rs1799983 and rs2070744 Polymorphisms in Patients with Unstable Angina. J Vasc Res. 2020;57(3):136–42. doi: 10.1159/000506160.