Association of Т174М polymorphism of the angiotensinogen gene with the higher risk of cerebral stroke in women


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Abstract

AIM. To study the association of M235T (rs699) and T174M (rs4762) polymorphisms of the angiotensinogen (AGT) gene with the risk of cerebral stroke (CS) in the Russians of the Central Chernozem Region. MATERIALS AND METHODS. A total of 638 DNA samples obtained from 353 patients with CS and 285 sex- and age-matched healthy individuals were examined. The polymorphisms were genotyped by polymerase chain reaction (T174M) and TaqMan allelic discrimination (M235T) assays. RESULTS. Heterozygous AGT 174TM genotype carriers were found to be at a higher risk for CS (odd ratio (OR)=1.52; 95% confidence interval (CI), 1.08-2.15; p=0.02). A gender-stratified analysis showed that the mutant 174M allele (OR=1.86; 95% CI, 1.14-3.03, p=0.01) and variant 174TM and 174MM genotypes (OR=1.86; 95% CI, 1.09-3.20; p=0.02) were associated with the higher risk of cerebral stroke in women. Conclusion. The association of AGT T174M polymorphism with the risk of CS was first found; but the higher risk of the disease in the carriers of variant alleles and genotypes was observed in the women only.

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Ассоциация полиморфизма Т174М гена ангиотензиногена с повышенным риском развития мозгового инсульта у женщин. - Резюме. Цель исследования. Изучение ассоциации полиморфизмов M235T (rs699) и T174M (rs4762) гена ангиотензиногена (AGT) с риском развития мозгового инсульта (МИ) у русских жителей Центрального Черноземья. Материалы и методы. Исследовали 638 образцов ДНК 353 пациентов с МИ и 285 здоровых индивидуумов соответствующего пола и возраста. Генотипирование полиморфизмов проводили методами полимеразной цепной реакции (T174M) и аллельной дискриминации с помощью TaqMan-зондов (M235T). Результаты. Выявлено, что у носителей гетерозиготного генотипа 174TM гена AGT повышен риск развития МИ (отношение шансов - ОШ - 1,52 при 95% доверительном интервале - ДИ - от 1,08 до 2,15; р=0,02). Стратифицированный анализ по полу показал, что мутантный аллель 174M (ОШ 1,86 при 95% ДИ от 1,14 до 3,03; р=0,01), а также вариантные генотипы 174TM и 174MM (ОШ 1,86 при 95% ДИ от 1,09 до 3,20; р=0,02) ассоциированы с повышенным риском развития МИ у женщин. Заключение. Впервые обнаружена связь полиморфизма T174M гена AGT с риском развития МИ, но повышенный риск развития заболевания у носителей вариантных аллелей и генотипов наблюдается только у женщин.
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References

  1. Lozano R., Naghavi M., Foreman K. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380 (9859): 2095-2128.
  2. Banerjee I., Gupta V., Ahmed T. et al. Inflammatory system gene polymorphism and the risk of stroke: a case-control study in an Indian population. Brain Res Bull 2008; 75 (1): 158-165.
  3. Мищенко Т.С., Овсянникова В.В., Лебединец В.В. Факторы риска и клинические особенности у больных с различными подтипами ишемического инсульта. Междунар мед журн 2011; 3: 27-32.
  4. Bevan S., Traylor M., Adib-Samii P. et al. Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke 2012; 43 (12): 3161-3167.
  5. Saidi S., Mallat S.G., Almawi W.Y., Mahjoub T. Association between renin-angiotensin-aldosterone system genotypes and haplotypes and risk of ischemic stroke of atherosclerotic etiology. Acta Neurol Scand 2009; 119 (6): 356-363.
  6. Atkinson J. Stroke, high blood pressure and the rennin-angiotensin-aldosterone system - new developments. Front Pharmacol 2011; 2 (22): 1-6.
  7. Nakajima T., Wooding S., Sakagami T. et al. Natural Selection and population history in the human angiotensinogen gene (AGT): 736 complete AGT sequences in chromosomes from around the world. Am J Hum Genet 2004; 74 (5): 898-916.
  8. Ludwig E.H., Borecki I.B., Ellison R.C. et al. Associations between candidate loci angiotensin-converting enzyme and angiotensinogen with coronary heart disease and myocardial infarction: the NHLBI Family Heart Study. Ann Epidemiol 1997; 7 (1): 3-12.
  9. Winkelmann B.R., Russ A.P., Nauck M. et al. Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease. Am Heart J 1999; 137: 698-705.
  10. Tiret L., Ricard S., Poirier O. et al. Genetic variation at the angiotensinogen locus in relation to high blood pressure and myocardial infarction: the ECTIM Study. J Hypertens 1995; 13: 311-317.
  11. Yamakawa-Kobayashi K., Arinami T., Hamaguchi H. Absence of association of angiotensinogen gene T235 allele with increased risk of coronary heart disease in Japanese. Lancet 1995; 346 (8973): 515.
  12. Barley J., Markus H., Brown M., Carter N. Lack of association between angiotensinogen polymorphism (M235T) and cerebrovascular disease and carotid atheroma. J Hum Hypertens 1995; 9 (8): 681-683.
  13. Usacheva M.A., Nasedkina T.V., Ikonnikova A. Y. et al. Association study of renin-angiotensin system genes and hemostasis system genes with ischemic stroke among Russians of Central Russia. Mol Biol (Mosk) 2012; 46 (2): 214-223.
  14. Sethi A.A., Tybjaerg-Hansen A., Gronholdt M.L. et al. Angiotensinogen mutations and risk for ischemic heart disease, myocardial infarction, and ischemic cerebrovascular disease. Six case-control studies from the Copenhagen City Heart Study. Ann Intern Med 2001; 134 (10): 941-954.
  15. Brenner D., Labreuche J., Poirier O. et al. Renin-angiotensin-aldosterone system in brain infarction and vascular death. Ann Neurol 2005; 58: 131-138.
  16. Vialykh E.K., Solidolova M.A., Bushueva O.Iu. et al. Catalase gene polymorphism is associated with increased risk of cerebral stroke in hypertensive patients. Zh Nevrol Psikhiatr Im S S Korsakova 2012; 112 (8, pt 2): 3-7.
  17. Polonikov A.V., Solodilova M.A., Ivanov V.P. et al. A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors. Ter Arkh 2011; 83 (4): 55-60.
  18. Procopciuc L., Popescu T., Jebeleanu G. et al. Essential arterial hypertension and polymorphism of angiotensinogen M235T gene. J Cell Mol Med 2002; 6 (2): 245-250.
  19. Morsing P., Adler G., Brandt-Eliasson U. et al. Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin. Hypertension 1999; 33 (6): 1406-1413.
  20. Kamitani A., Rakugi H., Higaki J. et al. Enhanced predictability of myocardial infarction in Japanese by combined genotype analysis. Hypertension 1995; 25 (5): 950-953.
  21. Marciante K.D., Bis J.C., Rieder M.J. et al. Renin-angiotensin system haplotypes and the risk of myocardial infarction and stroke in pharmacologically treated hypertensive patients. Am J Epidemiol 2007; 166 (1): 19-27.
  22. Um J.Y., Moon K.S., Lee K.M. et al. Polymorphism of angiotensin-converting enzyme, angiotensinogen, and apolipoprotein E genes in Korean patients with cerebral infarction. J Mol Neurosci 2003; 21 (1): 23-28.
  23. Van Rijn M.J., Bos M.J., Isaacs A. et al. Polymorphisms of the rennin-angiotensin system are associated with blood pressure, atherosclerosis and cerebral white matter pathology. J Neurol Neurosurg Psychiatr 2007; 78 (10): 1083-1087.
  24. Wang B., Guo Q., Peng Y. et al. Association of AGT M235T and ACE I/D polymorphisms with the risk of ischemic stroke: meta-analysis in Han Chinese population. J Neurol Sci 2012; 320 (1-2): 79-84.
  25. Wang S., Zeng R., Lei L., Huang J. Angiotensinogen gene polymorphism and ischemic stroke in East Asians: a meta-analysis. Neural Regen Res 2013; 8 (13): 1228-1235.
  26. Liang X., Qiu J., Liu X. et al. Polymorphism of angiotensinogen gene M235T in myocardial infarction and brain infarction: a meta-analysis. Gene 2013; 529 (1): 73-79.
  27. Marcheselli S., Micieli G. Renin-angiotensin system and stroke. Neurol Sci 2008; 29 (2): 277-278.
  28. Goldstein L.B., Bushnell C.D., Adams R.J. et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42 (2): 517-584.
  29. Jeunemaitre X., Soubrier F., Kotelevtsev Y.V. et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71 (1): 169-180.
  30. Goldenberg I., Moss A.J., Ryan D. et al. Polymorphism in the angiotensinogen gene, hypertension, and ethnic differences in the risk of recurrent coronary events. Hypertension 2006; 48 (4): 693-699.
  31. Watkins W.S., Rohrwasser A., Peiffer A. et al. AGT genetic variation, plasma AGT, and blood pressure: An analysis of the Utah Genetic Reference Project pedigrees. Am J Hypertens 2010; 23 (8): 917-923.
  32. Rotimi C., Cooper R., Ogunbiyi O. et al. Hypertension, serum angiotensinogen and molecular variants of the angiotensinogen gene among Nigerians. Circulation 1997; 95 (10): 2348-2350.
  33. Liang B., Qin L., Wei H. et al. AGT M235T polymorphisms and ischemic stroke risk. J Neurol Sci 2013; 331 (1-2): 118-125.
  34. O'Donnell C.J., Lindpaintner K., Larson M.G. et al. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 1998; 97 (18): 1766-1772.
  35. Mohana V.U., Swapna N., Surender R.S. et al. Gender-related association of AGT gene variants (M235T and T174M) with essential hypertension-a case-control study. Clin Exp Hypertens 2012; 34 (1): 38-44.
  36. Oelkers W.K. Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids 1996; 61 (4): 166-171.
  37. Feldmer M., Kaling M., Takahashi S. et al. Glucocorticoid and estrogen responsive elements in the 5' flanking region of the rat angiotensinogen gene. J Hypertens 1991; 9 (11): 1005-1012.

Copyright (c) 2014 Stetskaia T.A., Bushueva O.I., Bulgakova I.V., Vialykh E.K., Shuteeva T.V., Biriukov A.E., Ivanov V.P., Polonikov A.V.

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