Genetic determinants of cardiovascular remodeling n Urbek patients with essential hypertension

Abstract

Aim. To study distribution of the incidence of polymorphic markers of the genes ACE (I/D), ANG (M235T), AT1R (A1166C), CYP11B2 (T344C) in patients with essential hypertension (EH) of Uzbek nationality; to determine carriage of gene combinations with detection of most unfavourable combinations associated with severity of cardiovascular remodeling.
Material and methods. We examined 172 Uzbek males with EH of the second-third degree, mean age 49.4 ± 7.8 years, mean duration of EH 6.5 ± 5.1 years. Polymorphism I/D, A1166C, M235T, T344C of genes ACE, AT1R, ANG, CYP11B2, respectively, was revealed in all the patients. The control group consisted of 60 Uzbek males matched by age. We performed echocardiography, duplex scanning of carotid arteries, dopplerography of the brachial artery, IEMA measurement of the level of vascular adhesion molecule VCAM-1S in blood serum, microalbuminuria in Micral-test. We isolated genome DNA, amplified polymorphic gene regions and analysed products of polymerase chain reaction.
Results. Distribution of polymorphic markers of the genes ACE, CYP11B2, ANG, AT1R in EH Uzbek patients corresponds to this in Europeans. In most cases (95.4%) there was primarily combined carriage of "destroying" alleles of the genes of renin-angiotensin-aldosteron system associated with synergetic impact on development of left ventricular hypertrophy (LVH) and vascular remodeling; combination of alleles D+235T is most unfavourable in relation to severity of LVH, vasoregulatory endothelial dysfunction and is associated with the highest thickness of intima-media complex of the carotid artery. The role of 235T allele of ANG gene is most important in development of LVH.
Conclusion. Severity of vasoregulatory endothelial dysfunction is associated with carriage of both 235T allele of ANG gene and 1166C allele of AT1R gene, in the latter case aggravated by significant adhesion of vascular endothelium. Progression of atherosclerotic affection of the carotid arteries is associated more with carriage of D allele of ACE gene.

References

  1. Бебихов Д. В., Никоненко Т. А., Постнов А. Ю., Постнов Ю. В. Неменделевское наследование артериальной гипертензии: повторяющиеся последовательности ДНК как кандидаты на роль геномных детерминант. Кардиология 2001; 6: 34-40.
  2. O'Shaughnessy K. M. The genetics of essential hypertension. Br. J. Clin. Pharmacol. 2001; 51(1): 5-11.
  3. Кобалава Ж. Д., Котовская Ю. В., Чистяков Д. А. и др. Клинико-генетические детерминанты гипертрофии левого желудочка у больных эссенциальной гипертонией. Кардиология 2001; 7: 39-44.
  4. Минушкина Л. О., Затейщикова А. А., Хатченкова Н. В. и др. Активность ренин-альдостероновой системы и особенности структуры и функции миокарда левого желудочка у больных артериальной гипертонией. Кардиология 2000; 9: 23-26.
  5. Lee Y. A., Lindpaintner K. Role of the cardiac renin-angiotensin system in hypertensive cardiac hypertrophy. Eur. Heart J. 1993; 14 (suppl. J): 42-48.
  6. Devereux R. B., Reichek N. Echocardiographic determination of left ventricular mass in man; anatomic validation of the method. Circulation 1977; 55: 613-618.
  7. Teiccholtz L. E., Kruelen T., Herman M. V., Gorlin R. Problems in echocardiographic volume determination. Am. J. Cardiol. 1976; 37: 7-11.
  8. Беленков Ю. Н., Мареев В. Ю., Агеев Ф. Т. Эндотелиальная дисфункция при сердечной недостаточности. Кардиология 2001; 5: 100-104.
  9. Kupari M., Hautanen A., Lankinen L. et al. Association between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation 1998; 97: 569-575.
  10. Срожиддинова Н. З. Журн. клин. и теорет. мед. 2007; 3: 10-15.
  11. Елисеева М. Р., Абдуллаева Г. Ж., Срожиддинова Н. З. и др. Молекулярно-генетические аспекты ремоделирования сердечно-сосудистой системы и эффективности фармакотерапии при эссенциальной гипертонии. Кардиология СНГ 2006; 1: 27-36.
  12. Хамидуллаева Г. А., Елисеева М. Р., Срожиддинова Н. З., Абдуллаева Г. Ж. Особенности распределения полиморфных маркеров генов ренин-ангиотензин-альдостероновой системы, связь с гипертрофией левого желудочка у больных эссенциальной гипертонией узбекской национальности. Кардиология 2007; 4: 54-58.
  13. Кобалава Ж. Д., Котовская Ю. В., Чистяков Д. А. и др. Клинико-генетические детерминанты гипертрофии левого желудочка у больных эссенциальной гипертонией. Кардиология 2001; 7: 39-44.
  14. Bonnardeaux A., Davies E., Jeimemaitre X. et al. Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension Hypertension 1994; 24: 63-69.
  15. Brand E., Chatelain N., Mulatero P. et al. Structural analysis and evaluation of the aldosterone synthase gene in hypertension. Hypertension 1998; 32: 198-204.
  16. O'Donnell C. J., Lindpainther K., Larson M. G. et al. The ACE deletion insertion polymorphism and hypertension: on association analysis in the Framingham Heart Study. In: College cardiology, 46-th Annual scientific session 1997; 724-732.
  17. Iwai N., Ohmichi N., Nakamura Y. et al. DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation 1994; 90: 2622-2628.
  18. Карпов З. С., Пузырев К. В., Павлюкова Е. Н. Молекулярно-генетический анализ гипертрофии миокарда левого желудочка. Кардиология 2001; 6: 25-30.
  19. Kimura M., Yokota M., Fujimura T. et al Association of a deletion polymorphism of the angiotensin-converting enzyme gene with left ventricular hypertrophy in Japanese women with essential hypertension; multicenter study of 1,919 subjects. Cardiology 1997; 88: 309-314.
  20. Ueno H., Takata M., Yasumoto K. et al. Angiotensin-converting enzyme gene polymorphism and geometric patterns of hypertensive left ventricular hypertrophy. Jpn Heart J. 1999; 40: 589-598.
  21. Jeunemaitre X., Soubrier F., Kotelevtsev Y. V. et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71(1): 169-180.
  22. Kuznetsova T., Staessen J. A., Thijs L. et al. Left ventricular mass in delation to genetic variation in angiotensin II receptors, renin system genes, and sodium excretion. Circulation 2004; 110; 2644-2650.
  23. Rasmussen L. J., North K. E., Gu C. Ch. et al. A population association study of angiotensinogen polymorphisms and haplotypes with left ventricular phenotypes. Hypertension 2005; 46: 1294-1299.
  24. Castellano M., Muisan M. L., Beschi M. et al. Angiotensin II type 1 receptor A/C 1166 polymorphism. Relationship with blood pressure and cardiovascular structure. Hypertension 1996; 28: 1076-1080.
  25. Kikuya M., Sugimoto K., Katsuya T. et al. A/C 1166 gene polymorphism of the angiotensin II type 1 receptor (ATI) and ambulatory blood pressure: the Ohasama Study. Hypertens. Res. 2003; 26(2): 141-145.
  26. Takami S., Katsuya T., Rakugi H. Angiotensin II type 1 receptor gene polymorphism is associated with increased of left ventricular mass but not with hypertension. Am. J. Hypertens. 1998; 11(pt 1): 316-321.
  27. Davies E., Holloway C. D., Ingram M. C. et al. Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. Hypertension 1999; 33: 703-707.
  28. Tiago A. D., Badenhorst D., Nkeh B. et al. Impact of renin-angiotensin-aldosterone system gene variants on the severity of hypertension in patients with newly diagnosed hypertension. Am. J. Hypertens. 2003; 16: 1006-1010.
  29. Tamaki S., Iwai N., Tsujita Y., Kinoshita M. Genetic polymorphism of CYP11B2 gene and hypertension in Japanese. Hypertension 1999; 33(pt 2): 266-270.
  30. Stella P., Bigatti G., Tizzoni L. et al. Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension. J. Am. Coll. Cardiol. 2004; 43(2): 265-270.
  31. Kupari M., Hautanen A., Lankinen L. et al. Association between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation 1998; 97: 569-575.
  32. Van Geel P. P., Pinto Y. M., Voors A. A. et al. Angiotensin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries. Hypertension 2000; 35: 717-721.
  33. Минушкина Л. О., Затейщиков Д. А., Сидоренко Б. А. Генетические аспекты регуляции эндотелиальной функции при артериальной гипертонии. Кардиология 2000; 3: 68-74.

Copyright (c) 2009 Eliseeva M.R., Srozhidinova N.Z., Khamidullaeva G.A., Abdullaeva G.Z., Eliseeva M.R., Srozhidinova N.Z., Khamidullaeva G.A., Abdullaeva G.Z.

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