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Atrial fibrillation (AF) is the most common heart rhythm disturbance. It is believed that the primary form of AF is genetically determined in most cases, but the genetic component cannot be excluded in the secondary form of AF. AF is a heterogeneous disease and many authors proved its relationship with other genetic heart disease. In most cases, certain combinations of polymorphisms of different genes promote the development of AF. The study of genes of renin-angiotensin-aldosterone system (RAAS) is especially important, because the role of this system in AF pathogenesis is currently studding most intensively. These studies are of great practical interest, as associative effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the prevention of AF is revealed. RAAS blockers are able not only to reduce the risk of new-onset AF in hypertensive and normotensive patients but also prevent recurrence of AF. Furthermore, experimental studies showed that RAAS blockers prevent not only the remodeling of the left ventricle, and also the left atrium, pointing to the pathogenesis of AF. So, screening for susceptibility genes and the study of their polymorphism is currently an important focus in the study of AF.

About the Authors

A. V. Kuskaeva
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky. Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia
Russian Federation

S. Yu. Nikulina
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky. Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia
Russian Federation

A. A. Chernova
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky. Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia
Russian Federation

N. V. Aksyutina
Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky. Partizana Zheleznyaka ul. 1, Krasnoyarsk, 660022 Russia
Russian Federation


1. Feinberg W.M., Blackshear J.L., Laupacis A. et al. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med 1995;155(5):469-73

2. Skuratova MA, Duplyakov DV, Zemlyanova ME. Genetic aspects of the development of atrial fibrillation. Vestnil Aritmologii 2011; 63: 66-70. In Russian (Скуратова М.А., Дупляков Д.В., Землянова М.Е. Генетические аспекты развития фибрилляции предсердий. Вестник Аритмологии 2011;63: 66-70).

3. Kopecky S.L., Gersh B.J., McGoon M.D. et al. The natural history of lone atrial fibrillation. A population-based study over three decades. N Engl J Med 1987;317(11):669-74

4. Fuster V., Ryden L.E., Cannom D.S. et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation - executive summary: a report of the American College of Cardiology. American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006;48:854.

5. Wong C.X., Stiles M.K., John B. et al. Direction-dependent conduction in lone atrial fibrillation. Heart Rhythm 2010;7(9):1192-9

6. Parvez B., Darbar D. Lone AF - etiologic factors and genetic insights into pathophysiology. J Atr Fibrillation 2010;1(12):675-84.

7. Calkins H., Brugada J., Cappato R. et al. 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design. Heart Rhythm 2012;4(9):632-17

8. Marcus G.M., Smith L.M., Vittinghoff E. et al. A first-degree family history in lone atrial fibrillation patients. Heart Rhythm 2008;5(6):826-30

9. Johnson J.N., Tester D.J., Perry J. et al. Prevalence of early-onset atrial fibrillation in congenital long QT syndrome. Heart Rhythm 2008; 5(5):704-9.

10. Chen L.Y., Herron K.J., Tai B.C., Olson T.M. Lone atrial fibrillation: influence of familial disease on gender predilection. J Cardiovasc Electrophysiol 2008; 19(8):802-6.

11. Arnar D.O., Thorvaldsson S., Manolio T.A. et al. Familial aggregation of atrial fibrillation in Iceland. Eur Heart J 2006;27(6):708-12.

12. Ellinor P.T., Yoerger D.M., Ruskin J.N., MacRae C.A. Familial aggregation in lone atrial fibrillation. Hum Genet 2005; 118(2):179-84.

13. Shulman VA, Nikulina SY, Isachenko OO, et al. Genetic aspects of atrial fibrillation. Vestnik Aritmologii 2007; 46: 57-60.In Russian (Шульман В.А, Никулина С.Ю, Исаченко О.О. и др. Генетические аспекты фибрилляции предсердий. Вестник Аритмологии 2007;46:57-60).

14. Wolff L. Familial auricular fibrillation. N Engl J Med 1943;229:396-7.

15. Gould W.L. Auricular fibrillation; report on a study of a familial tendency, 1920-1956. AMA Arch Intern Med 1957;100(6): 916-26.

16. Phair W.B. Familial atrial fibrillation. Can Med Assoc J 1963; 89:1274-6.

17. Gillor A., Korsch E. Familial manifestation of idiopathic atrial flutter. Monatsschr Kinderheilkd 1992;140(1):47-50.

18. Tikanoja T., Kirkinen P., Nikolaev K. et al. Familial atrial fibrillation with fetal onset. Jpn Heart J 1998;79(2):195-7.

19. Brugada R., Tapscott T., Czernuszewicz G.Z. et al. Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997;336(13):905-11.

20. Ellinor P.T., Shin J.T., Moore R.K. et al. Locus for atrial fibrillation maps to chromosome 6q14-16. Circulation 2003;107(23):2880-3.

21. Hodgson-Zingman D.M., Karst M.L., Zingman L.V. et al. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation. N Engl J Med 2008;359(2):58-165.

22. Kääb S., Darbar D., Van Noord C. et al. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J 2009;30(7):813-19.

23. Gudbjartsson D.F., Arnar D.O., Helgadottir al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 2007;448(7151):353-7.

24. Oberti C., Wang L., Li L. et al. Genome-wide linkage scan identifies a novel genetic locus on chromosome 5p13 for neonatal atrial fibrillation associated with sudden death and variable cardiomyopathy. Circulation 2004;110(25):3753-9.

25. Darbar D., Hardy A., Haines J.L. Roden D.M. Prolonged signal-averaged P-wave duration as an intermediate phenotype for familial atrial fibrillation. J Am Coll Cardiol 2008;51(11):1083-9.

26. Tsai C.T., Lai L.P., Hwang J.J. et al. Molecular genetics of atrial fibrillation. J Am Coll Cardiol 2008;52(4):241-50.

27. Volders P.G., Zhu Q., Timmermans C. et al. Mapping a novel locus for familial atrial fibrillation on chromosome 10p11-q21. Heart Rhythm 2007;4(4):469-75.

28. Chen Y.H., Xu S.J., Bendahhou S. et al. KCNQ1 gain-of-function mutation in familial atrial. Science 2003;299(5604):251-4.

29. Benjamin E.J., Rice K.M., Arking D.E. et al. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet 2009;41(8):879-81.

30. Gudbjartsson D.F., Holm H., Gretarsdottir S. et al. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat Genet 2009;41(8):876-8.

31. Plaster N.M., Tawil R., Tristani-Firouzi M. et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 2001;105:511-9.

32. Ehrlich J.R., Hohnloser S.H., Nattel S. Role of angiotensin system and effects of its inhibition in atrial fibrillation: clinical and experimental evidence. Eur Heart J 2006;27(5):512-8.

33. Iravanian S., Dudley S.C. The renin–angiotensin–aldosterone system (RAAS) and cardiac arrhythmias. Heart Rhythm 2008; 5(6):12-7.

34. Novo G., Guttilla D., Fazio G. et al. The role of the renin–angiotensin system in atrial fibrillation and the therapeutic effects of ACE-Is and ARBS. Br J Clin Pharmacol 2008;66(3):345-51.

35. Ehrlich J.R., Hohnloser S.H., Nattel S. Role of angiotensin system and effects of its inhibition in atrial fibrillation: clinical and experimental evidence. Eur Heart J 2006;27(5):512-8.

36. Liu T., Korantzopoulos P., Xu G. et al. Association between angiotensin-converting enzyme insertion/deletion gene polymorphism and atrial fibrillation: a meta-analysis. Europace 2011.13(3):346-54.

37. Sayed-Tabatabaei F.A., Oostra B.A., Isaacs A. et al. ACE polymorphisms. Circulation Res 2006;98(9): 1123-33.

38. Zintzaras E., Raman G., Kitsios G., Lau J. Angiotensin-converting enzyme insertion/deletion gene polymorphic variant as a marker of coronary artery disease: a meta-analysis. Arch Intern Med 2008;168(10):1077-89.

39. Rudnicki M., Mayer G. Significance of genetic polymorphisms of the renin-angiotensin-aldosterone system in cardiovascular and renal disease. Pharmacogenomics 2009;10(3):463-76.

40. Danser A.H., Derkx F.H., Hense H.W. et al. Angiotensinogen (M235T) and angiotensin-converting enzyme (I/D) polymorphisms in association with plasma renin and prorenin levels. J Hypertens 1998;16(12 Pt2):1879-83.

41. Jones A., Dhamrait S.S., Payne J.R. et al. Genetic variants of angiotensin II receptors and cardiovascular risk in hypertension. Hypertension 2003;42(4):500-6.

42. Silvestrova GA, Golubeva AA, Pogoda TV, et al. Polymorphic gene markers of the renin-angiotensinaldosterone system and gene NO-synthase in the diagnosis of hypertension in men of the Central region of Russia. Arterialnaya Gipertenziya 2008; 5: 40-5. In Russian (Сильвестрова Г.А., Голубева А.А., Погода Т.В. и др. Полиморфные маркеры генов ренин-ангиотензин-альдостероновой системы и гена NO-синтазы в диагностике артериальной гипертензии у мужчин Центрального региона России. Артериальная Гипертензия 2008;5:40-5).

43. Ravn L.S., Benn M., Nordestgaard B.G. et al. Angiotensinogen and ACE gene polymorphisms and risk of atrial fibrillation in the general population. Pharmacogenet Genomics 2008;18(6):525-33.

44. Topal N.P., Ozben B., Hancer V.S. et al. Polymorphisms of the angiotensinconverting enzyme and an-giotensinogen gene in patients with atrial fibrillation. Journal of Renin-Angiotensin-Aldosterone System 2011;12(4):549-56.

45. Tsai C.T., Hwang J.J., Chiang F.T. et al. Renin-angiotensin system gene polymorphisms and atrial fibrillation: a regression approach for the detection of gene-gene interactions in a large hospitalized population. Cardiology 2008;111(1):1-7.

46. Yashu W., Ying L., Jinqi F. et al. Association study of the angiotensinconverting enzyme (ACE) gene rs4340 and rs4343 polymorphism with atrial fibrillation. Heart 2011;97(21):56-7.

47. Huang M., Gai X., Yang X. et al. Functional polymorphisms in ACE and CYP11B2 genes and atrial fibrillation in patients with hypertensive heart disease. Clin Chem Lab Med 2009;47(1):32-7.

48. Gensini F., Padeletti L., Fatini C. et al. Angiotensin-converting enzyme and endothelial nitric oxide syn-thase polymorphisms in patients with atrial fibrillation. Pacing Clin Electrophysiol 2003;26(1 Pt2):295-8.

49. Jiang M.H., Su Y.M., Tang J.Z. et Angiotensin- converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension. Clinics 2013;68(11):1428-32.

50. Watanabe H., Kaiser D.W., Makino S. et al. ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: Implications for electrical remodeling. Heart Rhythm 2009;6(9):1327-32.

51. Fatini C., Sticchi E., Gensini F. et al. Lone and secondary nonvalvular atrial fibrillation: role of a genetic susceptibility. Int J Cardiol 2007;120(1):59-65.

52. Darbar D., Motsinger A.A., Ritchie M.D. et al. Polymorphism modulates symptomatic response to an-tiarrhythmic drug therapy in patients with lone atrial fibrillation. Heart Rhythm 2007;4(6):743-9.

53. Ma R., Li X., Su G. et al. Angiotensin-converting enzyme insertion/deletion gene polymorphisms associated with risk of atrial fibrillation: A meta-analysis of 23 case-control studies. Journal Of The Renin-Angiotensin-Aldosterone System 2015;16(4):793-800.

54. Xiao P., Ling Z., Woo K. et al. Renin-angiotensin system - related gene polymorphisms are associated with risk of atrial fibrillation. Am Heart J 2010;160(3):496-505.

55. Ueberham L., Bollmann A., ShoemakerGenetic M.B. et al. ACE I/D polymorphism and recurrence of atrial fibrillation after catheter ablation. Circulation. Arrhythmia and Electrophysiology 2013;6(4): 732-7.

56. Zhang X.L., Wu L.Q., Liu X. et al. Association of angiotensin-converting enzyme gene I/D and CYP11B2 gene 344T/C polymorphisms with lone atrial fibrillation and its recurrence after catheter ablation. Exp Ther Med 2012;4(4):741-7.

57. Hou S., Lu Y., Huang D. et al. Association of atrial fibrillation with gene polymorphisms of connexin 40 and angiotensin II receptor type 1 in Chongming adults of Shanghai. Int J Clin Exp Med 2015;8(7):11803-10.

58. Wang Q.S., Li Y.G., Chen X.D. et al. Angiotensinogen polymorphisms and acquired atrial fibrillation in Chinese. J Electrocardiol 2010;43(4):373-7.

59. Wang Q., Hu X., Li S. et al. Association of the angiotensinogen M235T polymorphism with recurrence after catheter ablation of acquired atrial fibrillation. J Renin Angiotensin Aldosterone Syst 2015;16(4):888-97.

60. Wang H., Teng Y., Wang K. et al. The M235T polymorphism in the angiotensinogen gene and atrial fibrillation: A meta-analysis. J Renin Angiotensin Aldosterone Syst 2015;16(3):647-52.

61. Belluzzi F., Sernesi L., Preti P. et al. Prevention of recurrent lone atrial fibrillation by the angiotensin II converting enzyme inhibitor ramipril in normotensive patients. J Am Coll Cardiol 2009;53(1):24-9.

62. Tayebjee M.H., Creta A., Moder S. et al. Impact of angiotensin-converting enzyme-inhibitors and an-giotensin receptor blockers on long-term outcome of catheter ablation for atrial fibrillation. Europace 2010;12(11):1537-42.

63. Klemm H.U., Heitzer T., Ruprecht U. et al. Impact of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on the long-term outcome after pulmonary vein isolation for paroxysmal atrial fibrillation. Cardiology 2010;117(1):14-20.

64. Kumagai K., Nakashima H., Urata H. et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003;41(12):2197-204.

65. Nakashima H., Kumagai K., Urata H. et al. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 2000;101(22):2612-7.

For citation:

Kuskaeva A.V., Nikulina S.Y., Chernova A.A., Aksyutina N.V. GENETIC PREDICTORS OF ATRIAL FIBRILLATION. Rational Pharmacotherapy in Cardiology. 2016;12(3):331-336.

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