A protective effect of Gly272Ser polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors

Abstract

Aim. To study associations of C825T (rs5443) and G272S (rs16932941) polymorphisms of GNB3 gene in Russian population of the Central Chernozem region with essential hypertension (EH) risk; to elicit the role of environmental risk factors in realization of EH predisposition in this gene genotypes carriers.
Material and methods. We studied DNA samples obtained from 205 EH patients and 207 healthy individuals. EH patients were treated in Kursk hospitals. Genotyping of GNB3 gene polymorphisms was conducted by polymerase chain reaction and restriction analysis.
Results. Prevalence of 825T allele of GNB3 gene in EH patients and healthy individual was 0.334 and 0.295, respectively, of 272S allele - 0.037 and 0.058, respectively. We found no significant differences by prevalence of genotypes of gene GNB3 polymorphisms C825T and G272S in EH patients and healthy individuals. Non-smoking carriers of 272GS genotype had a low risk of EH (OR 0.42 in 95% CI from 0.18 to 0.97; p = 0.04). Smokers had no protective effect of this genotype. The protective effect of 272GS genotype was also found in individuals with low or moderate alcohol drinking habits (OR 0.29 in 95% CI from 0.11 to 0.77, p = 0.02) and in individuals without chronic exposure to stress (OR 0.29 in 95% CI from 0.09 to 0.91, p = 0.04). In contrast, hard drinkers and patients exposed to chronic stress had no protective effect of heterozygous genotype 272GS of gene GNB3.
Conclusion. G272S polymorphism of GNB3 gene can be considered as a new genetic marker of predisposition to EH. The protective effect depends of environmental factors associated with high risk to develop EH.

About the authors

Aleksey Valer'evich Polonikov

Email: polonikov@rambler.ru

Mariya Andreevna Solodilova

Email: m-solodilova@rambler.ru

Vladimir Petrovich Ivanov

Email: medbiol@kursknet.ru

Aleksandr Mikhaylovich Shestakov

Email: shestakof@yandex.ru

Dmitriy Vladimirovich Ushachev

Email: okb@sovtest.ru

Ekaterina Konstantinovna Vyalykh

Email: kate-yours@mail.ru

Oksana Vladimirovna Vasil'eva

Email: vovpost@kursknet.ru

Natal'ya Vladimirovna Polyakova

Email: medbiol@kursknet.ru

Vladimir Vladimirovich Antsupov

Email: medbiol@kursknet.ru

Valentina Aleksandrovna Kabanina

Email: medbiol@kursknet.ru

Yana Sergeevna Kupriyanova

Irina Viktorovna Bulgakova

Mikhail Alekseevich Kozhukhov

Email: okb@sovtest.ru

Dmitriy Sergeevich Tevs

Email: okb@sovtest.ru

A V Polonikov

State Medical University, Kursk

State Medical University, Kursk

M A Solodilova

State Medical University, Kursk

State Medical University, Kursk

V P Ivanov

State Medical University, Kursk

State Medical University, Kursk

A M Shestakov

Regional hospital, Kursk

Regional hospital, Kursk

D V Ushachev

Regional hospital, Kursk

Regional hospital, Kursk

E K Vyalykh

Regional hospital, Kursk

Regional hospital, Kursk

O V Vasilyeva

State Medical University, Kursk

State Medical University, Kursk

N V Polyakova

State Medical University, Kursk

State Medical University, Kursk

V V Antsupov

State Medical University, Kursk

State Medical University, Kursk

V A Kabanina

State Medical University, Kursk

State Medical University, Kursk

Ya S Kupriyanova

State Medical University, Kursk

State Medical University, Kursk

I V Bulgakova

State Medical University, Kursk

State Medical University, Kursk

M A Kozhukhov

Regional hospital, Kursk

Regional hospital, Kursk

D S Tevs

Regional hospital, Kursk

Regional hospital, Kursk

References

  1. Kearney P. M., Whelton M., Reynolds K. et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365 (9455): 217-223.
  2. Шальнова С. А., Баланова С. А., Константинов В. В. и др. Артериальная гипертония: распространенность, осведомленность, прием лекарственных препаратов и эффективность лечения среди населения Российской Федерации. Рос. кардиол. журн. 2006; 4: 45-50.
  3. Rossier B. C., Shild L. Epithelial sodium channel. Mendelian versus essential hypertension. Hypertension 2008; 52 (4): 595- 600.
  4. Orlov S. N., Postnov I. Y., Pokudin N. I. et al. Na+/H+ exchange and other ion transport systems in erythrocytes of essential hypertensives and spontaneously hypertensive rats: a comparative analysis. J. Hypertens. 1989; 7 (10): 781-788.
  5. Diez J., Alonso A., Garciandia A. et al. Association of increased Na+/H+ exchanger with renal Na+ retention in patients with essential hypertension. Am. J. Hypertens. 1995; 8 (2): 124- 132.
  6. Frolich O., Karmazyn M. The Na-H exchanger revisited: an update on Na-H exchange regulation and the role of the exchanger in hypertension and cardiac function in health and disease. Cardiovasc. Res. 1997; 36 (2): 138-148.
  7. Rosskopf D., Dusing R., Siffert W. Membrane sodium-proton exchange and primary hypertension. Hypertension 1993; 21 (2): 607-617.
  8. Schunkert H., Hense H. W., Doring A. et al. Association between a polymorphism in the G protein b3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension 1998; 32 (3): 510-513.
  9. Neves S. R., Ram P. T., Iyengar R. G protein pathways. Science 2002; 296 (5573): 1636-1639.
  10. Rosskopf D., Koch K., Habich C. et al. Interaction of Gbeta3s, a splice variant of the G-protein Gbeta3, with Ggamma- and Galpha-proteins. Cell. Signal. 2003; 15 (5): 479-488.
  11. Wettschureck N., Offermanns S. Mammalian G proteins and their cell type specific functions. Physiol. Rev. 2005; 85 (4): 1159-1204.
  12. Levine M. A., Modi W. S., O'Brien S. J. Chromosomal localization of the genes encoding two forms of the G-protein beta polypeptide, beta-1 and beta-3 in man. Genomics 1990; 8 (2): 380-386.
  13. Siffert W., Rosskopf D., Siffert G. et al. Association of a human G-protein beta3 subunit variant with hypertension. Nat. Genet. 1998; 18 (1): 45-48.
  14. Benjafield A. V., Jeyasingam C. L., Nyholt D. R. et al. G-protein b3 subunit gene (GNB3) variant in causation of essential hypertension. Hypertension 1998; 32 (6): 1094-1097.
  15. Hengstenberg C., Schunkert H., Mayer B. et al. Association between a polymorphism in the G protein beta3 subunit gene (GNB3) with arterial hypertension but not with myocardial infarction. Cardiovasc. Res. 2001; 49 (4): 820-827.
  16. Dong Y., Zhu H., Sagnella G. A. et al. Association between the C825T polymorphism of the G protein b3-subunit gene and hypertension in blacks. Hypertension 1999; 34 (6): 1193- 1196.
  17. Brand E., Herrmann S. M., Nicaud V. et al. The 825C/T polymorphism of the G-protein subunit beta3 is not related to hypertension. Hypertension 1999; 33 (5): 1175-1178.
  18. Ishikawa K., Imai Y., Katsuya T. et al. Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure. Am. J. Hypertens. 2000; 13 (2): 140-145.
  19. Tsai C. H., Yeh H. I., Chou Y. et al. G protein beta3 subunit variant and essential hypertension in Taiwan - a case-control study. Int. J. Cardiol. 2000; 73 (2): 191-195.
  20. Sartori M., Semplicini A., Siffert W. et al. G-protein beta3-subunit gene 825T allele and hypertension: a longitudinal study in young grade I hypertensives. Hypertension 2003; 42 (5): 909- 914.
  21. Renner W., Hoffman M. M., Grunbacher G. et al. G-protein beta3 subunit (GNB3) gene polymorphisms and cardiovascular disease: The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Atherosclerosis 2007; 192 (1): 108-112.
  22. Zeltner R., Delles C., Schneider M. et al. G-protein β3 subunit gene (GNB3) 825T allele is associated with enhanced renal perfusion in early hypertension. Hypertension 2001; 37 (3): 882.
  23. Siffert W., Forster P., Jöckel K. H. et al. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J. Am. Soc. Nephrol. 1999; 10 (9): 1921- 1930.
  24. Rosskopf D., Manthey I., Siffert W. Identification and ethnic distribution of major haplotypes in the gene GNB3 encoding the G-protein beta3 subunit. Pharmacogenetics 2002; 12 (3): 209-220.
  25. Rosskopf D., Busch S., Manthey I., Siffert W. G protein beta 3 gene: structure, promoter, and additional polymorphisms. Hypertension 2000; 36 (1): 33-41.
  26. Koch W. J., Hawes B. E., Allen L. F., Lefkowitz R. J. Direct evidence that Gi-coupled receptor stimulation of mitogen-activated protein kinase is mediated by G beta gamma activation of p21 ras. Proc. Natl. Acad. Sci. USA. 1994; 91 (26): 12706- 12710.
  27. Poch E., Gonzales D., Gomez-Angelats E. et al. G-protein β3 subunit variant and left ventricular hypertrophy in essential hypertension. Hypertension 2000; 35 (1, pt 2): 214-218.
  28. Bagos P. G., Elefsinioti A. L., Nikolopoulos G. K. et al. The GNB3 C825T polymorphism and essential hypertension: a meta-analysis of 34 studies including 14,094 cases and 17,760 controls. J. Hypertens. 2007; 25 (3): 487-500.
  29. Nefedova Y., Zukova A., Vinnik T. et al. Angiotension-adducin gene-gene interaction in hypertension development. Atherosclerosis 1999; 144 (suppl.): 73.
  30. Минушкина Л. О., Бражник В. А., Носиков В. В. и др. Ассоциация генетических факторов с клиническими особенностями гипертонической болезни у больных с отягощенным семейным анамнезом. Кардиология 2009; 2: 38-46.
  31. Карпов Р. С., Пузырев В. П., Кошельская О. А. и др. Полиморфные маркеры генов GNB3 (C825T), AGTR1 (A1166C) и ACE (A2350G и I/D) у больных артериальной гипертонией, сочетающейся с сахарным диабетом типа 2. Тер. арх. 2004; 6: 30-35.
  32. Siffert W. G protein polymorphisms in hypertension, atherosclerosis, and diabetes. Annu. Rev. Med. 2005; 56 (1): 17-28.
  33. Morris A. J., Malbon C. C. Physiological regulation of G protein-linked signaling. Physiol. Rev. 1999; 79 (4): 1373-1430.
  34. Siffert W., Rosskopf D., Moritz A. et al. Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J. Clin. Invest. 1995; 96 (2): 759-766.
  35. Pietruck F., Moritz A., Montemurro M. et al. Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated. Circ. Res. 1996; 79 (5): 974-983.

Copyright (c) 2011 Polonikov A.V., Solodilova M.A., Ivanov V.P., Shestakov A.M., Ushachev D.V., Vyalykh E.K., Vasil'eva O.V., Polyakova N.V., Antsupov V.V., Kabanina V.A., Kupriyanova Y.S., Bulgakova I.V., Kozhukhov M.A., Tevs D.S., Polonikov A.V., Solodilova M.A., Ivanov V.P., Shestakov A.M., Ushachev D.V., Vyalykh E.K., Vasilyeva O.V., Polyakova N.V., Antsupov V.V., Kabanina V.A., Kupriyanova Y.S., Bulgakova I.V., Kozhukhov M.A., Tevs D.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies