RISK OF ARTERIAL HYPERTENSION IN THE POPULATION OF WESTERN UKRAINE DEPENDING ON CLINICAL, GENDER, AND MOLECULAR-GENETIC PREDICTORS

Keywords: arterial hypertension, NOS3 (rs2070744), GNB3 (rs5443) genes, risks, anthropometric parameters, obesity

Abstract

Introduction. Nowadays, the number of adults with hypertension has doubled worldwide from 650 million in 1990 to 1.28 billion in 2019, mostly in low- and middle-income countries. Late diagnosis of the disease leads to increased morbidity, target organs damage, and early disability. Therefore, risk factors stratification for patients with hypertension is an important task of modern medicine.

Objective. To study the risk of essential arterial hypertension (EAH) in the population of Western Ukraine, taking into account anthropometric, clinical and demographic, gender and genetic factors (NOS3, rs2070744 and GNB3, rs5443).

Materials and methods. 100 patients with EAH and 48 apparently healthy individuals (the control group) participated in the study. All participants underwent clinical and laboratory examinations. Risk factors included a burdened anamnesis of cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), body mass index (BMI) in men (M) and women (W). GNB3 (rs5443) and NOS3 (rs2070744) genes genotyping was performed by real-time PCR.

Results. The EAH risk in the population generally increased due to the CVD burdened heredity regardless of the NOS3 (rs2070744) and GNB3 (rs5443) genes genotypes by almost 3–4.5 times, with the most pronounced correlation in the mutation C-allele carriers of the NOS3 gene and in T-allele carriers of the GNB3 gene [OR = 3.10–4.29; OR (95% CI): 1.03–13.77; p ≤ 0.041–0.005], due to DM2 – by 7–14 times [OR = 7.14–14.25; OR (95% CI): 1.0–127.2; p ≤ 0.043–0.006], due to increased WC (M > 102 cm, W > 88 cm) – by 3.5–17 times [OR = 3.45–16.67; OR (95% CI): 1.06–66.09; p ≤ 0.035–0.0001]. Gender analysis confirmed the association between increased risk of EAH and elevated WHR, but only for women (> 0.85 U) – by 4.5–51 times [OR = 4.44–51.33; OR (95% CI): 1.10–346.9; p ≤ 0.036–0.0001] in TT‑genotype carriers of the NOS3 gene and in the CC-genotype carriers of the GNB3 gene. Augmented BMI (> 25.0 kg/m2) also enhanced the EAH risk by more than 6–9 times [OR = 6.29–9.0; OR (95% CI): 1.0–83.07; p ≤ 0.034–0.011], but only in women with TT genotype of the NOS3 gene and the CC genotype of the GNB3 gene (rs5443) – by 5 times [OR = 4.80; OR (95% CI): 1.25–18.42; p = 0.019] and 11.5 times [OR = 11.50; OR (95% CI): 2.01–65.91; p = 0.004], respectively.

Conclusions. The risk of EAH in the Western Ukraine population increased with burdened CVD heredity regardless of genetic factors, DM2, elevated BMI, WC and WHR, but only in women, with the most pronounced correlation in the TT genotype carriers of NOS3 gene and CC genotype patients of GNB3 gene.

Author Biographies

Andriy R. Sydorchuk, Department of Physiology and Pathophysiology, Sumy State University, Medical Institute, Sumy, Ukraine

Aспірант кафедри фізіології і патофізіології з курсом медичної біології, Медичний інститут Сумського державного університету МОН України, 40000, вулиця Санаторна, 31, місто Суми;

e.mail: lsydorchuk@ukr.net

Victoria Yu. Harbuzova, Department of Physiology and Pathophysiology, Sumy State University, Medical Institute, Sumy, Ukraine

Професор, доктор біологічних наук, професор кафедри фізіології і патофізіології з курсом медичної біології, Медичний інститут Сумського державного університету МОН України, 40000, вулиця Санаторна, 31, місто Суми;

e.mail: v.garbuzova@med.sumdu.edu.ua

References

1. WHO.int. More than 700 million people with untreated hypertension. [online]. WHO. 2021. https://www.who.int/news/item/25-08-2021-more-than-700-million-people-with-untreated-hypertension. Accessed 22 December 2021.
2. Bin Zhou, Rodrigo M Carrillo-Larco, Goodarz Danaei, Leanne M Riley, et al. 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. The Lancet. 2021; 398(10304):957-980.
3. Tu N Nguyen, Clara K Chow. Global and national high blood pressure burden and control. The Lancet. 2021; 398(10304):932-933.
4. Unger T, Borghi C, Charchar F, Khan NA, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020;75(6):1334-1357.
5. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104.
6. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Di Angelantonio E, Franco OH, Halvorsen S, Hobbs FDR, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227-3337.
7. Tegegne BS, Man T, van Roon AM, Asefa NG, Riese H, Nolte I, Snieder H. Heritability and the Genetic Correlation of Heart Rate Variability and Blood Pressure in >29 000 Families: The Lifelines Cohort Study. Hypertension. 2020;76(4):1256-1262. doi: 10.1161/HYPERTENSIONAHA.120.15227.
8. Repchuk Y, Sydorchuk L, Fedoniuk L, Nebesna Z, Vasiuk V, Sydorchuk A, Iftoda O. 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.
9. Repchuk Y, Sydorchuk LP, Sydorchuk AR, Fedonyuk LY, Kamyshnyi O, Korovenkova O, Plehutsa IM, Dzhuryak VS, Myshkovskii YM, Iftoda OM, Sydorchuk RI. Blood pressure, obesity and di-abetes mellitus linkage with an-giotensinogen gene (AGT 704T>C/rs699) polymorphism in hypertensive patients. Bratislava Medical Journal. 2021; 122(10):715-720.
10. Semianiv M, Sydorchuk L, Fedonyuk L, Nebesna Z, Kamyshnyi O, Sydorchuk A, Vasiuk V, Dzhuryak V, Semianiv I, Sydorchuk R. Metabolic and Hormonal Prognostic Markers of Essential Arterial Hypertension Considering the Genes Polymorphism AGTR1 (rs5186) and VDR (rs2228570). Romanian Journal of Diabetes Nutrition and Metabolic Diseases. 2021;28 (3):284-91. https://www.rjdnmd.org/index.php/RJDNMD/article/view/1049.
11. 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.
12. 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.
13. 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.
14. Fattakhov N, Smirnova L, Atochin D, Parshukova D, Skuratovskaia D, Painter Q, Zatolokin P, Semke A, Litvinova L, Ivanova S. 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):2036-2046.
15. Misiak B, Krolik M, Kukowka A, Lewera A, Leszczynski P, Stankiewicz-Olczyk J, Slezak R. The Role of −786T/C Polymorphism in the Endothelial Nitric Oxide Synthase Gene in Males with Clinical and Biochemical Features of the Metabolic Syndrome. International Journal of Endocrinology 2011;2011:Article ID 458750.
16. 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):257-258.
17. 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):136-142.
Published
2022-03-29
How to Cite
Andriy R. Sydorchuk, & Victoria Yu. Harbuzova. (2022). RISK OF ARTERIAL HYPERTENSION IN THE POPULATION OF WESTERN UKRAINE DEPENDING ON CLINICAL, GENDER, AND MOLECULAR-GENETIC PREDICTORS. Eastern Ukrainian Medical Journal, 10(1), 33-41. https://doi.org/10.21272/eumj.2022;10(1):33-41