The role of gene polymorphisms associated with the functioning of the renin-angiotensin system in the development of arterial hypertension and preeclampsia

Hereditary predisposition is one of the risk factors for arterial hypertension. The renin-angiotensin-aldosterone system plays a key role in the pathogenesis of arterial hypertension. Previous studies have shown a correlation between the AGT and AGTR genes and the risk of developing arterial hypertension. The genes of the renin-angiotensin system are considered candidates for predisposition to preeclampsia. In our study, we examined the relationship between arterial hypertension (AH) and polymorphisms of the renin-angiotensin-aldosterone system genes: AGT: 704 T>C, AGT: 521 C>T, AGTR 1: 1166 A>C, and AGTR 2: 1675 G>A, among the European population of Moscow. The presence of the T allele of the AGT gene (T704C) has a protective effect on the development of AH. The CT and TT genotypes of the AGT gene (C 521T) are significantly more common in hypertensive patients, which may indicate a negative effect of the T allele on the development of hypertension. Carrying the CC genotype of the AGTR 1 gene (A1166C) may predispose to hypertension. It has been established that the presence of the G allele and the G allele.

1. Lyamina N.P., Nalivaeva A.V., Senchikhin V.N. Polymorphism of the AGT and AGTR1 genes and the severity of cardiovascular risk factors at a young age in masked and stable forms of arterial hypertension. Modern Problems of Science and Education. 2016; 4: 19. (In Russ.). URL: https://science-education.ru/ru/article/view?id=24878 (Аccessed on: 31.01.2026).

2. International Consortium for Blood Pressure Genome – Wide Association Studies et al, Genetic variants in novel pathways infl uence blood pressure and cardiovascular disease risk. // Nature. 2011 Sep 11; 478 (7367): 103–9. https://doi.org/10.1038/nature10405

3. Almazov V.A., Shvarts E.I., Shlyakhto E.V. Pathogenesis of Hypertensive Disease. The First Results of Molecular Genetic Research/ Arterial Hypertension. 2000; 6 (21): 7–15. (In Russ.). https://russjcardiol.elpub.ru/jour/article/view/2023?ysclid=ml2gqkc5si393144048 (Аccessed on: 31.01.2026).

4. Fedoseeva L.A. Expression of key genes of the renin-angiotensin system in hypertensive Nisag rats. Dissertation for the degree of Candidate of Biological Sciences. 2014. (In Russ.). https://www.icgbio.ru/wp-content/uploads/2022/04/fedoseevala.pdf?ysclid=ml2gtx3wvr581992129 (Аccessed on: 31.01.2026).

5. Charlton K. E., Steyn K., Levitt N. S. et al. Development and validation of a short questionnaire to assess sodium intake. Public Health Nutrition. 2008; 11 (01): 83–94. https://doi:10.1017/S1368980007000146

6. Jin JJ, Nakura J, Wu Z, Yamamoto M, Abe M, Chen Y, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T. Association of angiotensin II type 2 receptor gene variant with hypertension. Hypertens Res. 2003 Jul; 26 (7): 547–52. https://doi:10.1291/hypres.26.547

7. Agerholm-Larsen B., Nordestgaard B.G., Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol. 2000; 20 (2): 484–92. https://doi:10.1161/01.atv.20.2.484

8. Rosei E.A. Hypertension, atherosclerosis and LVH in ELSA. Blood Pressure. 1996; 5 (Suppl 4): 44–47. PMID: 8973783. https://pubmed.ncbi.nlm.nih.gov/8973783 (Аccessed on: 31.01.2026).

9. Nikitin A.G. Association study of a number of candidate genes with coronary heart disease. Abstract of the thesis for the degree of Candidate of Biological Sciences. 2008. (In Russ.). https://textarchive.ru/c-1130414-pall.html

10. Castellano M., Muiesan M. L., Beschi M. et al. Angiotensin II type 1 receptor gene A/C1166 polymorphism: relationships with blood pressure and cardiovascular structure. Hypertension. 1996; 28: 1076–1080. https://doi:10.1161/01.hyp.28.6.1076

11. Hajjar I., Sorond F., Hsu Y.H. Renin angiotensin system gene polymorphisms and cerebral blood fl ow regulation: the MOBILIZE Boston study. Stroke. 2010; 41 (4): 635–40. https://doi:10.1161/STROKEAHA.109.572669

12. Pilbrow A.P. et al. Angiotensinogen M235T and T174M gene polymorphisms in combination doubles the risk of mortality in heart failure. Hypertension, 2007; 49 (2): p. 322–7. https://doi:10.1161/01.HYP.0000253061.30170.68

13. Kotlovsky M. Yu., Kotlovskaya O.S., Yakimenko A.V. Study of the Relationship between the m235t Gene Mutation of Angiotensinogen and Hypertensive Disease/ Modern Problems of Science and Education.– 2016; 3: 197. https://science-education.ru/article/view?id=24868&ysclid=ml2hfh1eqc222075643 (Аccessed on: 31.01.2026).

14. Sethi A. A. et al. Angiotensinogen polymorphisms and elevated blood pressure in the general population: the Copenhagen City Heart Study. Hypertension, 2001; 37 (3): 875–81. https://doi:10.1161/01.hyp.37.3.875

15. Sorokina V.N., Pavlyushchik E.A., Chak T.A. et al. Association of m235t polymorphism of the agt gene with arterial hypertension in men. Military Medicine. 2016; 2: 56–59. https://elibrary.ru/item.asp?id=26525864&ysclid=ml2hj81l93869051716 (Аccessed on: 31.01.2026).

16. Poch E. et al. Molecular basis of salt sensitivity in human hypertension. Evaluation of renin – angiotensin-aldosterone system gene polymorphisms. Hypertension. 2001; 38 (5): 1204–1209. https://doi:10.1161/hy1101.099479

17. Xiaoyang L. Association of T174M polymorphism of angiotensinogen gene with essential hypertension: A meta-analysis / Xiaoyang L, Yang Z, Peng D, Hua D, Yi L, Qian Z. et al. Genetics and Molecular Biology. 2014; 37 (3): 473–9. https://doi:10.1590/s1415-47572014000400001

18. Shestakov A.M. Complex Molecular and Genetic Analysis of Polymorphism of Candidate Genes for Hypertensive Disease in the Population of Russian Residents of the Central Chernozem Region: PhD Thesis in Medicine. Moscow, 2010. 165 p. (In Russ.). http://www.dslib.net/genetika/kompleksnyj-molekuljarno-geneticheskij-analiz-polimorfizma-genov-kandidatov.html?ysclid=ml2ho0fk6m602266485 (Аccessed on: 31.01.2026).

19. Hata A., Namikawa C., Sasaki M., Sato K., Nakamura T., Tamura К., Lalouel J.M. Angiotensinogen as a risk factor for essential hypertension in Japan. J. Clin. Invest. 1994; 93: 1285–1287. https://doi:10.1172/JCI117083

20. Rosei E.A., Dal Palu C., Leonetti G. et al. Clinical results of the Verapamil in Hypertension and Atherosclerosis Study. VHAS Investigators. J. Hypertens 1997; 15: 1337–1344. https://doi:10.1097/00004872-199715110-00019

21. N. T. Chang, T.P. Shkurat. Association study of the T174M and M235T angiotensinogen gene variants with coronary artery disease in the Rostov population/ Epidemiology. 2010. Apr; 11: 63–77. (In Russ.). www.medline.ru

22. Jeunemaitre X., Inoue I., Williams Ch., Charru A., Ticket J., Powers M., Sharma A. P., Gimenez-RoqueploA.-P., Hata A., Corvol P., Lalouel J.-M. Am.J. Hum. Genet. 1997; 60: 1448–1460. https://doi:10.1086/515452

23. Caulfield M., Lavender P., Farrall M., Munroe P., Lawson M., Turner P., Clark A. II New Eng. J. Med. 1994; 330: 1629–1633. https://doi:10.1056/NEJM199406093302301

24. Martinez E., Puras A., Escribano J. et al. Threonines at position 174 and 235 of the angiotensinogen polypeptide chain are related to familial history of hypertension in a Spanish-Mediterranean population. Br.J. Biomed Sci. 2002; 59 (2): 95–100. https://doi:10.1080/09674845.2002.11783642

25. Rotimi C., Puras A., Cooper R. et al. Polymorphisms of rennin-angiotensin genes among Nigerians, Jamaicans, and African Americans. Hypertension. 1996 Mar; 27 (3 Pt 2): 558–63. https://doi:10.1161/01.hyp.27.3.558

26. Muzhenya D.V. Pathophysiological Role and Predictive Significance of the M235T Polymorphism of the Angiotensinogen Gene (AGT) in Heart Continuum Diseases (HCD). Bulletin of Adyghe State University. Series 4: Natural Sciences, Mathematics, and Technical Sciences. 2012; 1: 66–79. (In Russ.). URL: https://cyberleninka.ru/article/n/patofiziologicheskaya-rol-i-prognosticheskaya-znachimost-m235t-polimorfizma-gena-angiotenzinogena-agt-pri-boleznyah-serdechnogo (Аccessed on: 31.01.2026).

27. Pakhomya N.S., Uryasiev O.M., Shakhanov A.V. The Role of Polymorphisms of Certain Genes in the Development of Arterial Hypertension. Zemsky Doctor. 2014; 3–4: 21–24. (In Russ.). https://cyberleninka.ru/article/n/rol-polimorfizmov-nekotoryh-genov-v-realizatsii-arterialnoy-gipertenzii?ysclid=ml2ikjb11k9628856 (Аccessed on: 31.01.2026).

28. Karjalainen J., Kujala U., Stolt A., Mäntysaari M., Viitasalo M., Kainulainen K., Angiotensinogen Gene M235T Polymorphism Predicts Left Ventricular Hypertrophy in Endurance Athletes. J. Am. Coll. Cardiol. 1999; 34 (2): 494–499. https://doi:10.1016/s0735-1097(99)00199-0

29. Pontremoli R., Ravera M., Viazzi F., Nicolella C., Berruti V., Leoncini G., Giacopelli F., Bezante G.P., Sacchi G., Ravazzolo R., Deferrari G. Genetic Polymorphism of the Renin-Angiotensin System and Organ Damage in Essential Hypertension. Kidney Int. 2000; 57 (2): 561–569. https://doi:10.1046/j.1523-1755.2000.00876.x

30. Kobashi G., Hata A., Ohta K., Yamada H., Kato E.H., Minakami H., Fujimoto S., Kondo K. A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene. J. Hum. Genet. 2004; 49: 182–186. https://doi:10.1007/s10038-004-0129-4

31. Abdi R. et al., Angiotensin gene polymorphism as a determinant of posttransplantation renal dysfunction and hypertension. Transplantation. 2001; 72 (4): 726–9. https://doi:10.1097/00007890-200108270-00028

32. Unger T. The angiotensin type 2 receptor: variations on an enigmatic theme. J Hypertens. 1999; 17 (12 Pt 2): 1775–86. https://doi:10.1097/00004872-199917121-00001

33. Baudin B. Polymorphism in angiotensin II receptor genes and hypertension. Exp Physiol. 2005; 90 (3): 277–82. https://doi:10.1113/expphysiol.2004.028456

34. Wang W.Y., Zee R.Y., Morris B.J. Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Clin Gen. 1997; 51 (1): 31–4. https://doi:10.1111/j.1399-0004.1997.tb02410.x

35. Saab Y.B. et al. Renin-angiotensin-system gene polymorphisms and depression. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31 (5): 1113–8. https://doi:10.1016/j.pnpbp.2007.04.002

36. van de Wal R.M.A., van Veldhuisen D.J., van Gilst W.H., Voors A.A. Addition of an Angiotensin Receptor Blocker to Full-Dose ACE-Inhibition: Controversial or Common Sense? Eur. Heart J. 2005; 26 (): 2361–2367. https://doi:10.1093/eurheartj/ehi454

37. Hindorff L.A., Heckbert S.R., Tracy R., Tang Z., Psaty B., Edwards K., Siscovick D., Kronmal R., Nazar-Stewart V. Angiotensin II Type 1 Receptor Polymorphisms in the Cardiovascular Health Study: Relation to Blood Pressure, Ethnicity, and Cardiovascular Events. Am.J. Hypertens. 2002; 15 (): 1050–1056.

38. Levitsky S.N., Pervukhina O.A. The Role of Renin-Angiotensin System Gene Polymorphism in the Development of Cardiovascular Pathology. Vestnik NArFU. Ser.: Medical and Biological Sciences. 2016; 4: 30–39. (In Russ.). https://elibrary.ru/item.asp?id=27238972&ysclid=ml2iur0ct6665756804 (дата обращения: 31.01.2026).

39. Carey R. M. and Siragy H. M. Newly recognized components of the rennin -angiotensin system: potential roles in cardiovascular and renal regulation. Endocrinol. 2003; 24: 261–271. https://doi:10.1210/ER.2003-0001

40. Carstens N., van der Merwe L., Revera M. et al. Genetic variation in angiotensin II type 2 receptor gene infl uences extent of left ventricular hypertrophy in hypertrophic cardiomyopathy independent of blood pressure. J. Renin Angiotensin Aldosterone Syst. 2011; 12 (3): 274–80. https://doi:10.1177/1470320310390725

41. Medica I, Kastrin A, Peterlin B. Genetic polymorphisms in vasoactive genes and preeclampsia: a meta-analysis. Eur J. Obstet Gynecol Reprod Biol. 2007 Apr; 131 (2): 115–26. https://doi:10.1016/j.ejogrb.2006.10.005

42. Wang C, Zhou X, Liu H, Huang S. Three polymorphisms of renin-angiotensin system and preeclampsia risk. J. Assist Reprod Genet. 2020 Dec; 37 (12): 3121–3142. https://doi:10.1007/s10815-020-01971-8

43. Jeunemaitre X., Inoue I., Williams Ch., Charru A., Ticket J., Powers M., Sharma A. P., Gimenez-RoqueploA.-P., Hata A., Corvol P., Lalouel J.-M. Am.J. Hum. Genet. 1997; 60: 1448–1460. https://doi:10.1086/515452

44. Inagami T. Molecular biology and signaling of angiotensin receptors: an overview. J. Am. Soc. Nephrol. 1999; 10 (Suppl 11): S 2–S 7. https://pubmed.ncbi.nlm.nih.gov/9892133 (Аccessed on: 31.01.2026).