Genetic determinants of hypertension in two national cohorts of Mountain Shoria

Barbarash O.L.; Voevoda M.I.; Artamonova G.V.; Mulerova T.A.; Voropaeva Е.N.; Maksimov V.N.; Ogarkov M.Iu.

doi:https://doi.org/10.17116/terarkh201789968-77

Close metadata

Recommended articles:

The significance of exogenous nitrate and nitrite of plant origin for vascular health. Russian Journal of Preventive Medicine. 2024;(11):141-146

Predictors of Engagement and Active participation of Patients with Uncontrolled Hypertension in the Telehealth Surveillance Program. Russian Journal of Preventive Medicine. 2024;(12):37-43

Assessment of the Association Between Vitiligo and Autoimmune Thyroiditis Based on a Cross-Sectional Study. Russian Journal of Clinical Dermatology and Venereology. 2024;(6):684-690

Efficacy and tolerability of azilsartan combined with amlodipine and amlodipine monotherapy and combinations of amlodipine with other angiotensin II receptor blockers. Russian Cardiology Bulletin. 2024;(4-2):161-171

Risk factors and adverse outcomes of cardiovascular diseases in people with high normal blood pressure of the Ryazan region. (5-year prospective follow-up). Russian Journal of Preventive Medicine. 2025;(2):31-37

Diagnostics of hypertensive disorders in cardio-obstetrics: current state-of-affairs. Russian Journal of Human Reproduction. 2025;(1):63-77

Study of the levocarnitine efficacy for the treatment of moderate cognitive impairment in patients with hypertension. Russian Journal of Preventive Medicine. 2025;(4):45-50

Visceral obesity is a reversible factor in pathogenesis of major cardiovascular diseases. Russian Cardiology Bulletin. 2025;(3):11-16

Features of the interpretation of bodily sensations by patients with arterial hypertension. Russian Journal of Preventive Medicine. 2025;(10):82-87

Study of the effectiveness of the drug Elcarnitine in the correction of increased variability of arterial pressure in patients with hypertensive disease and cognitive dysfunction. Russian Journal of Preventive Medicine. 2025;(10):88-92

Abstract:

Aim. To estimate the prevalence of the genotypes of the candidate genes ACE (I/D, rs4646994), ADRB1 (Ser49Gly, A/G, rs1801252) ADRA2B (I/D), MTHFR (C677T, Ala222Val, rs1801133), and eNOS (4b/4a) and their association with hypertension in two ethnic groups of Mountain Shoria. Subjects and methods. A clinical and epidemiological study was conducted in a population compactly living in the hard-to-reach areas of Mountain Shoria (the settlements of Orton, Ust-Kabyrza, and Sheregesh of the Kemerovo Region). A continuous method was used to survey 1178 residents from the above settlements; the sample consisted of adults (aged 18 years and older), 565 people were genotyped. Results. The prevalence of hypertension among the population of Mountain Shoria was 42.3%. The incidence of this disease among the Shorians was lower (39.9%) than that among the representatives of non-indigenous people (46.1%). The ethnically justified peculiarities of the association of ADRA2B and ACE I/D polymorphisms with hypertension were established. There were fewer patients with hypertension among ACE ID and ADRA2B DD genotype carriers in the cohort of the Shorians than in that of the non-indigenous population: 40.6% versus 58.6% and 38.3% versus 64%, respectively. Conversely, there were more hypertensive patients among the carriers of the homozygous ACE DD genotype in the native ethnic group (60%) than in the non-indigenous one (37.1%). Conclusion. Adverse prognostic ACE DD, ADRB1 AA, MTHFR TT, and eNOS 4a/4a genotypes were more frequently observed in the non-indigenous ethnic groups; the ADRA2B DD genotype was more common in the native population. Hypertension was associated with the ACE DD, МTHFR CT, and ADRB1 AA genotypes in the native ethnic group and with the ACE ID genotype in the non-indigenous population.

Keywords:

ethnos

hypertension

candidate genes

associations

I/D polymorphism

endothelial synthase gene

Authors:

Barbarash O.L.

Kemerovskaia oblastnaia klinicheskaia bol'nitsa

SPIN RSCI: 5373-7620
Scopus AuthorID: 56699731800
ResearcherID: A-4834-2017
ORCID: 0000-0002-4642-3610

Voevoda M.I.

Research Institute of Therapy and Prophylactic Medicine, Siberian Branch of the Russian Academy of Medical Sciences;
City Clinical Hospital No1, Novosibirsk, Russia

Artamonova G.V.

Institution Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo

SPIN RSCI: 3972-2791
Scopus AuthorID: 36980033200
ResearcherID: S-6079-2016
ORCID: 0000-0003-2279-3307

Mulerova T.A.

FGBU "Nauchno-issledovatel'skiĭ institut kompleksnykh problem serdechno-sosudistykh zabolevaniĭ" SO RAMN, Kemerovo

Voropaeva Е.N.

Research Institute of Internal and Preventive Medicine, Novosibirsk, Russia

Maksimov V.N.

Research Institute of Therapy, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk

Ogarkov M.Iu.

Novokuznetskiĭ gosudarstvennyĭ institut usovershenstvovaniia vracheĭ Minzdrava Rossii

Close metadata

References:

Chazova IE, Ratovа LG, Boitsov SA, Nebieridze DV. Diagnosis and treatment of hypertension (Recommendations for the management of arterial hypertension Russian Medical Society of Arterial Hypertension and Society of Cardiology of the Russian Federation). Sistemnye gipertensii. 2010;3:5-26. (In Russ.).
Oganov RG, Timofeeva TN, Koltunov IE. Epidemiology of hypertension in Russia. The results of the Federal monitoring 2003—2010. Kardiovasculyarnaya terapiya i profilactica. 2011;1:9-14. (In Russ.).
Ageenkova OA. The results of epidemiological studies of hypertension prevalence among residents of the city of Smolensk. Sovremennye problemy nauki i obrazovaniya. 2014; 1:125-177. (In Russ.).
Boitsov SA. Ten years of searching for the genetic basis of hypertension: challenges and prospects. Arterialnaya gipertenziya. 2004;8(5):157-160. (In Russ.).
Linchak RM. Genetic aspects of hypertension. Vestnik nacionalnogo mediko-hirurgicheskogo centra im. N.I. Pirogova. 2007;1(2):126-132. (In Russ.).
Binder A. Identification of genes for a complex trait: examples from hypertension. Curr Pharm Biotechnol. 2006;7(1):1-13. https://doi.org/10.2174/138920106775789610
Cowley AWJr. The genetic dissection of essential hypertension. Nat Rev Genet. 2006;7(11):829-840. https://doi.org/10.1038/nrg1967
Orlova NV, Sitnikov VF, Chukaeva II, Prohin AV. The study of genetic conditions of hypertension as a risk factor for cardiovascular disease. Medicinskiy almanach. 2011;3(16):81-84. (In Russ.).
Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, Belmont JW, Boudreau A, Hardenbol P, Leal SM, Pasternak S, Wheeler DA, Willis TD, Yu F. A second generation human haplotype map of over 3.1 million SNPs. Nature. 2007;449(7164):851-861. https://doi.org/10.1038/nature06258
Sethupathy P, Collins F. MicroRNA target site polymorphisms and human disease. Trends Genet. 2008;24(10):489-497. https://doi.org/10.1016/j.tig.2008.07.004
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, Sham PC. PLINK: a toolset for whole-genome association and population based linkage analysis. Am J Hum Genet. 2007;81(3):559-575. https://doi.org/10.1086/519795
Avila-Vanzzini N, Posadas-Romero C, Gonzalez-Salazar Mdel C, Maass-Iturbide C, Melendez-Ramirez G, Perez-Mendez O, Valle-Mondragon Ldel, Masso-Rojas F, Lopez EV, Herrera-Bello H, Fernandez RV, Cruz-Robles D. The ACE I/D polymorphism is associated with nitric oxide metabolite and blood pressure levels in healthy Mexican men. Arch Cardiol Mex. 2015;85(2):105-110. https://doi.org/10.1016/j.acmx.2014.12.005
Rolim T, Cancino J, Zucolotto V. A nanostructured genosensor for the early diagnosis of systemic arterial hypertension. Biomed Microdevices. 2015;17(1):3. https://doi.org/10.1007/s10544-014-9911-z
Hu DC, Zhao XL, Shao JC, Wang W, Qian J, Chen AH, Zhang HQ, Guo H, Jiang J, Li HY. Interaction of six candidate genes in essential hypertension. Genet Mol Res. 2014;13(4):8385-8395. https://doi.org/10.4238/2014.october.20.14
Ji L, Cai X, Zhang L, Fei L, Wang L, Su J, Lazar L, Xu J, Zhang Y. Association between polymorphisms in the renin-angiotensin-aldosterone system genes and essential hypertension in the Han Chinese population. PLoS One. 2013;8(8):e72701. https://doi.org/10.1371/journal.pone.0072701
Niu S, Zhang B, Zhang K, Zhu P, Li J, Sun Y, He N, Zhang M, Gao Z, Li X, Simayi A, Ge J, Cong M, Zhou W, Qiu C. Synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system on essential hypertension in Kazakhs in Xinjiang. Clin Exp Hypertens. 2015;38(1):63-70. https://doi.org/10.3109/10641963.2015.1060985
Singh M, Singh AK, Singh S, Pandey P, Chandra S, Gambhir IS. Angiotensin-converting enzyme gene I/D polymorphism increases the susceptibility to hypertension and additive diseases: A study on North Indian patients. Clin Exp Hypertens. 2016;38(3):305-311. https://doi.org/10.3109/10641963.2015.1107085
Gao Y, Lin Y, Sun K, Wang Y, Chen J, Wang H, Zhou X, Fan X, Hui R. Orthostatic blood pressure dysregulation and polymorphisms of β-adrenergic receptor genes in hypertensive patients. J Clin Hypertens (Greenwich). 2014;16(3):207-213. https://doi.org/10.1111/jch.12272
Kong H, Li X, Zhang S, Guo S, Niu W. The β1-adrenoreceptor gene Arg389Gly and Ser49Gly polymorphisms and hypertension: a meta-analysis. Mol Biol Rep. 2013;40(6):4047-4053. https://doi.org/10.1007/s11033-012-2482-2
Iwamoto Y, Ohishi M, Yuan M, Tatara Y, Kato N, Takeya Y, Onishi M, Maekawa Y, Kamide K, Rakugi H. β-Adrenergic receptor gene polymorphism is a genetic risk factor for cardiovascular disease: a cohort study with hypertensive patients. Hypertens Res. 2011;34(5):573-577. https://doi.org/10.1038/hr.2010.281
Peng Y, Xue H, Luo L, Yao W, Li R. Polymorphisms of the beta1-adrenergic receptor gene are associated with essential hypertension in Chinese. Clin Chem Lab Med. 2009;47(10):1227-1231. https://doi.org/10.1515/cclm.2009.276
Ghogomu SM, Ngolle NE, Mouliom RN, Asa BF. Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon. Genet Mol Res. 2016;15(1):28. https://doi.org/10.4238/gmr.15017462
Yun L, Xu R, Li G, Yao Y, Li J, Cong D, Xu X, Zhang L. Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population. Medicine (Baltimore). 2015;94(52):e2389. https://doi.org/10.1097/md.0000000000002389
Nassereddine S, Kassogue Y, Korchi F, Habbal R, Nadifi S. Association of methylenetetrahydrofolate reductase gene (C677T) with the risk of hypertension in Morocco. BMC Res Notes. 2015;8(1):775. https://doi.org/10.1186/s13104-015-1772-x
Seidlerovа J, Filipovsky J, Mayer OJr, Kuсerovа A, Pesta M. Association between endothelial NO synthase polymorphisms and arterial properties in the general population. Nitric Oxide. 2015;44:47-51. https://doi.org/10.1016/j.niox.2014.11.016
Snapir A, Scheinin M, Groop LC, Orho-Melander M. The insertion/deletion variation in the α2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction, but may modify the risk for hypertension in sib-pairs from families with type 2 diabetes. Cardiovasc Diabetol. 2003;2:15.
Lima JJ, Feng H, Duckworth L, Wang J, Sylvester JE, Kissoon N, Garg H. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism. 2007;56(6):757-765. https://doi.org/10.1016/j.metabol.2007.01.007
Salimi S, Firoozrai M, Nourmohammadi I, Shabani M, Mohebbi A. Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran. Indian J Med Res. 2006;124(6):683-688.
Baranov VS, Ivashchenko TE, Baranova EV. The genetic passport — the basis of individual and predictive medicine. SPb.: Izd-vo N-L; 2009. (In Russ.).
Gorbunova VN. Genetics and epigenetics commensal disease. Aekologicheskaya genetika. 2010;8(4):39-43. (In Russ.).
Danser AH, Schalekamp MA, Bax WA, Van den Brink AM, Saxena PR, Riegger JA, Schunkert H. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation. 1995;92(6):1387-1388. https://doi.org/10.1161/01.cir.92.6.1387
Shulutko BI. Hypertension. SPb.: Sotis; 2001:98-108. (In Russ.).
Fox CS, Heard-Costa NL, Vasan RS, Murabito JM, D’Agostino RB, Atwood LD. Genomewide Linkage Analysis of Weight Change in the Framingham Heart Study. J Clin Endocrinol Metab. 2005;15:3197-3201. https://doi.org/10.1210/jc.2004-1752
Karaulova YuL, Pavlov AV, Moiseev VS. The study of the clinical and genetic determinants of left ventricular hypertrophy in patients with arterial hypertension and hypertrophic cardiomyopathy. Praktikuyushiy vrach. 2006;1:58-63. (In Russ.).
Zee RY, Bennett CL, Schrader AP, Morris BJ. Frequencies of variants of candidate genes in different age groups of hypertensives. Clin Exp Pharmacol Physiol 1994;21(11):925-930. https://doi.org/10.1111/j.1440-1681.1994.tb02468.x
Chiang FT, Lai ZP, Chern TH. Lack of association of the angiotensin converting enzyme polymorphism with essential hypertension in a Chinese population. Am J Hypertens. 1997;10(2):197-201. https://doi.org/10.1016/s0895-7061(96)00345-7
Maeda Y, Ikeda U, Ebata H, Hojo Y, Seino Y, Hayashi Y, Kuroki S, Shimada K. Angiotensin-converting enzyme gene polymorphism in hypertensive individuals with parental history of stroke. Stroke. 1996;27(9):1521-1523. https://doi.org/10.1161/01.str.27.9.1521
O’Donnel CJ, Lindpainter K, Larson MG, Rao VS, Ordovas JM, Schaefer EJ, Myers RH, Levy D Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framyngham Heart Study. Circulation. 1998;97(18):1766-1772. https://doi.org/10.1161/01.cir.97.18.1766
Glavnik N, Petrovic D. M235T polymorphism of the angiotensinogen gene and insertion/deletion polymorphism of the angiotensin-1 converting enzyme gene in essential arterial hypertension in Caucasians. Folia Biol (Praha). 2007;53(2):69-70.
Goncharova LN, Birlukova DV, Fedotkina LK. Insertion-deletion polymorphism of the angiotensin-converting enzyme in patients with familial hypertension indigenous population of the Republic of Mordovia. Vestnik Sankt-Peterburgskogo universiteta. 2009;1:26-29. (In Russ.).
Fatini C, Guazzelli R, Manetti P, Battaglini B, Gensini F, Vono R, Toncelli L, Zilli P, Capalbo A, Abbate R, Gensini GF, Galanti G. RAS genes influence exercise-induced left ventricular hypertrophy: an elite athletes study. Med Sci Sports Exerc. 2000;32(11):1868-1872.
Baitasova NB, Rysmendiev AZ. The genotypes of angiotensin-converting enzyme gene in patients with coronary artery disease - persons of Kazakh and Uygur nationalities. Klinicheskaya medicina. 2002;1:23-24. (In Russ.).
Miloserdova OP, Slominskii PA, Tarskaya LA. Polymorphic markers AGT and ACE genes in Yakuts. The lack of association with the blood pressure level. Genetika. 2001;37(5):712-715. (In Russ.).
Aquilante CL, Yarandi NH, Cavallari LH, Andrisin TE, Terra SG, Lewis JF, Hamilton KK, Johnson JA. β-Adrenergic receptor gene polymorphisms and hemodynamic response to dobutamine during dobutamine stress echocardiography. The Pharmacogenomics Journal. 2008;8(6):408-415. https://doi.org/10.1038/sj.tpj.6500490
Levin MC, Marullo S, Muntaner O, Andersson B, Magnusson Y. The myocardium_protective Gly-49 variant of the beta1-adrenergic receptor exhibits of constitutive activity and increased desensitization and down regulation. J Biol Chemistry. 2002;277(34):30429-30435. https://doi.org/10.1074/jbc.m200681200
Babenko AYu, Kostareva AA, Grinyova EN. Contribution common single nucleotide polymorphisms β1-adrenoceptor gene in changes in the cardiovascular system in thyrotoxicosis. Klinicheskaya i aexperimentalnaya tireoidologiya. 2014;10(2):22-31. (In Russ.).
Ranade K, Jorgenson E, Sheu W, Pei D, Hsiung CA, Chiang F, Botstein D, Risch N. A Polymorphism in the b1-adrenergic receptor is associated with resting heart rate. Am J Hum Genet. 2002;70(4):935-942. https://doi.org/10.1086/339621
Nieminen T. Effects of polymorphisms in beta1-adrenoceptor and alpha-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study. J Appl Physiol. 2006;100(2):507-511. https://doi.org/10.1152/japplphysiol.00899.2005
Suzuki N, Matsunaga T, Nagasumi K, Yamamura T, Shihara N, Moritani T, Ue H, Fukushima M, Tamon A, Seino Y, Tsuda K, Yasuda K. Alpha(2B)-adrenergic receptor deletion polymorphism associates with autonomic nervous system activity in young healthy Japanese. J Clin Endocrinol Metab. 2003;88(3):1184-1187. https://doi.org/10.1210/jc.2002-021190
Snapir A, Heinonen P, Tuomainen TP, Alhopuro P, Karvonen MK, Lakka TA, Nyyssönen K, Salonen R, Kauhanen J, Valkonen V-P, Pesonen U, Koulu M, Scheinin M, Salon JT. An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events. J Am Coll Cardiol. 2001;37(6):1516-1522. https://doi.org/10.1016/s0735-1097(01)01201-3
Vasudevan R, Ismail P, Stanslas J. Association of Insertion/Deletion Polymorphism of Alpha-Adrenoceptor Gene in Essential Hypertension with or without Type 2 Diabetes Mellitus in Malaysian Subjects. Int J Biol Sci. 2008;4(6):362-367. https://doi.org/10.7150/ijbs.4.362
Zhang H, Li X, Huang J, Li Y, Thijs L, Wang Z, Lu X, Cao K, Xie S, Staessen JA, Wang JG. Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population. J Hypertens. 2005;23(12):2201-2207. https://doi.org/10.1097/01.hjh.0000189869.48290.91
Baldwin CT, Schwartz F, Baima J, Burzstyn M, DeStefano AL, Gavras I, Handy DE, Joost O, Martel T, Manolis A, Nicolaou M, Bresnahan M, Farrer L, Gavras H. Identification of a polymorphic glutamic acid stretch in the alpha2B-adrenergic receptor and lack of linkage with essential hypertension. Am J Hypertens. 1999;12(9):853-857. https://doi.org/10.1016/s0895-7061(99)00070-9
Etzel JP, Rana BK, Wen G, Parmer RJ, Schork NJ, O’Connor DT, Insel PA. Genetic variation at the human alpha2B-adrenergic receptor locus: role in blood pressure variation and yohimbine response. Hypertension. 2005;45(6):1207-1213. https://doi.org/10.1161/01.hyp.0000166721.42734.49
Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998;64(3):169-172. https://doi.org/10.1006/mgme.1998.2714
Fetisova IN, Dobrolubov AS, Lipin MA, Polyakov AV. Polymorphism of genes of folate metabolism and disease in humans. Vestnik novych medicinskych technologiy. 2007;10(1):71-73. (In Russ.).
Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000;151(9):862-877. https://doi.org/10.1093/oxfordjournals.aje.a010290
Kalashnikova EA, Kokarovceva SN. The Association of hereditary thrombophilia factors to miscarriage in women in the Russian population. Med Genetika. 2005;8:386-391. (In Russ.).
Borodulin VB, Shevchenko OV, Bychkov EN. The value of genetic mutations in the development of metabolic disorders in hypertensive patients. Saratovskiy nauchno-medicinskiy gurnal. 2012;3(8):751-756. (In Russ.).
Metzger IF, Sertório JTC, Tanus-Santos JE. Modulation of nitric oxide formation by endothelial nitric oxide synthase gene haplotypes. Free Radical Biology and Medicine. 2007;43(6):987-992. https://doi.org/10.1016/j.freeradbiomed.2007.06.012
Wang XL, Mahoney MC, Sim AS, Wang J, Wang J, Blangero J, Almasy L, Badenhop RB, Wilcken DE. Genetic contribution of the endothelial constitutive nitric oxide synthase gene to plasma nitric oxide levels. Arterioscler Thromb Vasc Biol. 1997;17(11):3147-3153. https://doi.org/10.1161/01.atv.17.11.3147
Bairova TA, Dolgich VV Relationship polymorphism of endothelial nitric oxide synthase and hypertension in populations of Eastern Siberia. Bulleten Vostochno-Sibirskogo nauchnogo centra SO RAMN. 2007;3:64-65. (In Russ.).
Granath B, Taylor RR, van Bockxmeer FM, Mamotte CD. Lack of evidence for association between endothelial nitric oxide synthase gene polymorphisms and coronary artery disease in the Australian Caucasian population. J Cardiovasc Risk. 2001;8(4):235-241. https://doi.org/10.1177/174182670100800408
Nakagami H, Ikeda U, Maeda Y, Yamamoto K, Hojo Y, Kario K, Kuroki S, Shimada K. Coronary artery disease and endothelial nitric oxide synthase and angiotensin-converting enzyme gene polymorphisms. J Thromb Thrombolysis. 1999;8(3):191-195.