Genetic markers ofcardiovascular risk factors and arterial hypertension among indigenous populations of Mountain Shoria

Objective. To study the prevalence of the genetic risk factors and their role in the formation of hypertension and its risk factors among indigenous population of Mountain Shoria (Shors).

Design and methods. A clinicalepidemiological study of Mountain Shoria indigenous populations at isolated regions was undertaken. We examined 395 people by continuous method, the sample included adult population (aged 18 years and older). We studied anthropometric data, blood lipids, and polymorphisms of the genes ADRB1 (Ser49Gly, A/G, rs1801252) ADRA2B (I/D), ACE (I/D), eNOS (4a/4b) and MTHFR (C677T, Ala222Val, rs1801133).

Results. Mean levels of triglycerides, total cholesterol, very low density lipoproteins and atherogenic index were higher among people with homozygous DD genotype ADRA2B gene. D allele of the ADRA2B gene was found 2,8‑times more frequently among Shors with obesity in comparison to the population with normal weight. There is a 7,9‑time higher relative risk to detect D allele of the ACE gene among people with hypercholesterolemia than among people with normal levels of total cholesterol, and it is 11,2 times higher in group with hyperbetacholesterolemia than in group with normal levels of low density lipoprotein cholesterol. A allele homozygotes of the ADRB1 gene have 1,6 times higher risk of hypertension development in comparison with G allele homozygotes and heterozygotes.

Conclusions. Ther is a relation between Ser49Gly polymorphism of ADRB1 gene with atherogenicity index, I/D polymorphism ADRA2B gene with triglyceride level, low density lipoprotein cholesterol, atherogenic index, I/D polymorphism of ACE gene and the levels of total cholesterol and low density lipoprotein cholesterol. D allele of ADRA2B gene is associated with obesity, and abnormal fat distribution. An allele of ADRB1 gene is associated with the higher relative risk of hypertension progression in Shor population.

1. Оганов Р. Г., Тимофеева Т. Н., Колтунов И. Е. Эпидемиология артериальной гипертонии в России. Результаты Федерального мониторинга 2003–2010 гг. Кардиоваскулярная терапия и профилактика. 2011;1:9–13. [Oganov RG, Timofeeva TN, Koltunov IE. Epidemiology of hypertension in Russia. The results of the Federal monitoring 2003–2010. Kardiovaskulyarnaya Terapiya i Profilaktica = Cardiovascular therapy and prevention. 2011;1:9–13. In Russian].

2. Appel LJ. ASH position paper: dietary approaches to lower blood pressure. J Clin Hypert. 2009;11(7):358–368.

3. Nаbеr CК, Siffеr W. Gеnеtics оf humаn аrtеriаl hyреrtеnsiоn. Minеrvа Mеd. 2004;5(5):347–356

4. Qi Y, Niu W, Zhou W, Hou S, Qiu C. Cоrrеlаtiоn bеtwееn аngiоtеnsinоgеn gеnе роlymоrрhisms аnd еssеntiаl hyреrtеnsiоn in Chinеsе рорulаtiоn. J Hum Hyреrtеns. 2008;22(2):147–150.

5. Бойцов С. А. Десять лет поиска генетической основы гипертонической болезни: трудности и перспективы. Артериальная гипертензия. 2004;8(3):157–160. [Boytsov SA. Ten years of searching for the genetic basis of hypertension: challenges and prospects. Arterial’naya Gipertenziya = Arterial Hypertension. 2004;8(3):157–160. In Russian].

6. Bianchi G, Ferrari P, Staessen JA. Adducin polymorphism: detection and impact on hypertension and related disorders hypertension. Hypertension. 2005;45(3):331–340.

7. Wolff B, Grabe HJ, Schluter C, Popowski K, Völzke H, Lüdemann J et al. Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample. J Hypertens. 2005;23(7):1361–1366.

8. Wowern F, Bengtsson K, Lindblad U. Functional vari ant in the alpha.2B adrenoceptor gene, a positional candidate on chromosome 2, associates with hypertension. Hypertension. 2004;43(3):592–597.

9. Deng AY. Genetic basis of polygenic hypertension. Human molecular genetics. 2007;16(2):195–202.

10. Zivко M, Кusеc R, Gаlеsić К. Imраct оf аngiоtеnsincоnvеrting еnzymе gеnе роlymоrрhism оn рrоtеinuriа аnd аrtеriаl hyреrtеnsiоn. Аnthrороlоgy. 2013;37(3):765–770.

11. Кishimоtо T. еNОS Glu298 Аsр роlymоrрhism аnd hyреrtеnsiоn in а cоhоrt study in Jараnеsе. Рrеvеntivе Mеd. 2004;39 (5):927–931.

12. Cоwlеy АW. Thе gеnеtic dissеctiоn оf еssеntiаl hyреrtеnsiоn. Nаturе Rеv Gеnеtics. 2006;7(11):829–840.

13. Еichlеr ЕЕ. Missing hеritаbility аnd strаtеgiеs fоr finding thе undеrlying cаusеs оf cоmрlех disеаsе. Nаt Rеv Gеnеt. 2010;11 (6):446–450.

14. 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;24(2):15.

15. Lima JJ, Feng H, Duckworth L, Wang J, Sylvester JE, Kissoon N et al. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism. 2007;56(6):757–765.

16. 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.

17. Snapir A, Heinonen P, Tuomainen TP, Alhopuro P, Karvonen MK, Lakka TA et al. 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.

18. Wolff B, Grabe HJ, Schluter C, Popowski K, Völzke H, Lüdemann J et al. Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample. J Hypertens. 2005;23(7):1361–1366.

19. Vasudevan R, Ismail P, Stanslas J Shamsudin N, Ali AB. 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.

20. Baldwin CT, Schwartz F, Baima J, Burzstyn M, DeStefano AL, Gavras I et al. 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.

21. Etzel JP, Rana BK, Wen G, Parmer RJ, Schork NJ, O'Connor DT et al. Genetic variation at the human alpha2Badrenergic receptor locus: role in blood pressure variation and yohimbine response. Hypertension. 2005;45(6):1207–1213.

22. Heinemann P, Koulu M, Pesonen U. Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects. J Clin Endocrinol Metab. 1999;84(7):2429–2433.

23. 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;90(6):3197–3201.

24. Penesova A, Cizmarova E, Kvetnansky R, Koska J, Sedlakova B, Krizanova O. Insertion/deletion polymorphism on ACE gene is associated with endothelial dysfunction in young patients with hypertension. Horm Metab Res. 2006;38(9): 592–597.

25. 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.

26. Fatini C, Guazelli R, Manetti P, Battaglini B, Gensini F, Vono R et al. RAS genes influence exercise-induced left ventricular hypertrophy: an elite athletes study. Med Sci Sports Exerc. 2000;32 (11):1868–1872.

27. Nieminen T, Lehtimki T, Laiho J, Rontu R, Niemelä K, Kööbi T et al. 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.

28. Карпов Р. С., Пузырев К. В., Павлюкова Е. Н. Молекулярно-генетический анализ гипертрофии миокарда левого желудочка. Кардиология. 2001;6:25–30. [Karpov RS, Puzyrev KV, Pavlyukova EN. Molecular genetic analysis of left ventricular hypertrophy. Kardiologiya = Cardiology. 2001;6:25–30. In Russian].

29. Tong Y, Yin X, Wang Z, Zhan F, Zhang Y, Ye J et al. A tailed primers protocol to identify the association of eNOS gene variable number of tandem repeats polymorphism with ischemic stroke in Chinese Han population by capillary electrophoresis. Gene. 2013;517(2):218–223.

30. 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.

31. Nakagami H, Ikeda U, Maeda Y, Yamamoto K, Hojo Y, Kario K et al. Coronary artery disease and endothelial nitric oxide synthase and angiotensin-converting enzyme gene polymorphisms. J Thromb Thrombolysis. 1999;8(3):191–195.