Investigation of genetic factors leading to cardiovascular diseases in persons with risk of sudden cardiac death



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Abstract

About 85% of all sudden death are of cardiological origin. Predisposition to sudden cardiac death is known for the young and adult patients with a hereditary heart disease that can cause sudden cardiac arrest. The purpose of the work was to study the genetic predisposition for cardiovascular diseases in people with a risk of sudden cardiac death. We examined patients aged 19,7±2,1 years with a risk of sudden cardiac death based on specific complaints and medical history, and considering the known markers of the life-threatening arrhythmias. Of the 1000 patients, 167 with a risk of sudden cardiac death were selected according to the questionnaire. In 80 randomly selected patients from this group, gene polymorphisms associated with the development of thrombophilia and hypertension were studied by real time PCR, and in 59 patients the polymorphisms of genes associated with impaired carbohydrate and lipid metabolism were studied. A number of differences were revealed according to the standard 12-channel electrocardiography in comparison with practically healthy individuals. In the study of genetic factors predisposing the development of thrombophilia, hypertension, type 2 diabetes mellitus, lipid metabolism disorders, a high percentage of hetero- and homozygous individuals was revealed by the risk allele of the PAI-1 (83.3%), ITGA2 (69.2%), AGT genes (72.5%), NOS3 (58.8%), PON1 (56%), LEPR (64.3%). The data obtained indicate a significant role of genetic factors in the development of sudden cardiac death, and the synergistic effect of genes, as a result of which the presence of a risk allele in one gene can enhance the expression of another gene.

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About the authors

V. A Kachnov

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

S. N Koliubaeva

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

V. V Tyrenko

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

O. A Nagibovich

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

V. S Chirsky

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

O. V Protasov

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

L. A Myakoshina

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

A. S Buntovskaya

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

A. E Trandina

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

E. I Koreshova

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

M. I Eliseeva

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

O. G Brazhnikova

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

T. S Sveklina

S.M. Kirov Military Medical Academy

Email: ksnwma@mail.ru
Saint-Petersburg, Russia

References

  1. Tester D.J., Ackerman M.J. Genetic testing for potentially lethal, highly treatable inherited cardiomyopathies/channelopathies in clinical practice. Circulation 2011; 123(9): 1021-37.
  2. Fernandez-Falgueras A., Sarquella-Brugada G., Brugada J. et al. Cardiac channelopathies and sudden death: recent clinical and genetic advances. Biology 2017; 6(4): 7.
  3. Brion M., Sobrino B., Martinez M. et al. Massive parallel sequencing applied to the molecular autopsy in sudden cardiac death in the young. Forensic Science Int.: Genetics 2015; 18: 160-70.
  4. Magi S., Lariccia V., Maiolino M. et al. Sudden cardiac death: focus on the genetics of channelopathies and cardiomyopathies. J. Biomed. Science 2017; 24(1): 56.
  5. Колюбаева С.Н. Генетические предикторы внезапной смерти. Известия Воен.-мед. акад. 2017; 36: 14-22. [Kolyubayeva S.N. Genetic predictors of sudden death. News Military-medical. acad. 2017; 36: 14-22].
  6. Романенко В.В., Романенко З.В. Внезапная сердечная смерть: причины, патофизиология, диагностика, лечение, профилактика. Мед. новости 2012; 6: 29-36.
  7. Бокерия О.Л., Калысов К.А. Медикаментозное лечение внезапной сердечной смерти. Анналы Аритмологии 2013; 10(2): 101-10.
  8. Шляхто Е.В., Арутюнов Г.П., Беленков Ю.Н. Национальные рекомендации по определению риска и профилактике внезапной сердечной смерти. 2-е изд. М.: ИД «МеДпрактИка-М»; 2018.
  9. Christiaans I., Birnie E., Bonsel G.J. et al. Manifest disease, risk factors for sudden cardiac death, and cardiac events in a large nationwide cohort of predictively tested hypertrophic cardiomyopathy mutation carriers: determining the best cardiological screening strategy. European Heart J. 2011; 32(9): 1161-70.
  10. Ašić A., Salazar R., Storm N. et al. Population study of thrombophilic markers and pharmacogenetic markers of warfarin prevalence in Bosnia and Herzegovina. Croat. Med. J. 2019; 60(3): 212-20.
  11. Jankun J., Kondray V., Skrzypczak-Jankun E. Analysis of the inhibition of PAI-1 by metal theaflavin complexes and their degradation products. Int. J. Molecular Med. 2013; 31 (5): 1153-8.
  12. Wôjcik M., De La Morena-Barrio M.E., Michalik J. et al. A series of 10 Polish patients with thromboembolic events and antithrombin deficiency: two new c.1154-1 G>C and c.1219-534 A>G SERPINC1 gene splicing mutations. Blood Coagul Fibrinolysis 2019; 30(5): 193-8.
  13. De la Morena-Barrio M.E., Lôpez-Gâlvez R., Martinez-Martinez I. et al. Defects of splicing in antithrombin deficiency. Res. Pract. Thromb. Haemost. 2017; 1(2): 216-22.
  14. Santoso S., Kunicki T.J., Kroll H. et al. Association of the platelet glycoprotein la C807T gene polymorphism with nonfatal myocardial infarction in younger patients. Blood 1999; 93: 2449-53.
  15. Asselta R., Duga S., Tenchini M.L. The molecular basis of quantitative fibrinogen disorders. J. Thromb. Haemost. 2006; 4(10): 2115-29.
  16. Asselta R., Spena S., Duga S. et al. Molecular genetics of quantitative fibrinogen disorders. Cardiovasc. Hematol. Agents Med. Chem. 2007; 5(2): 163-73.
  17. Paraboschi E., Duga S., Asselta R. Fibrinogen as a Pleiotropic Protein Causing Human Diseases: The Mutational Burden of Aα, Bβ, and y Chains. Int. J. Mol. Sci. 2017; 18(12): 2711.
  18. Ehret G. Genes for preeclampsia: an opportunity for blood pressure genomics. Hypertension 2018; 72(2): 285-6.
  19. Rossi G.P., Ceolotto G., Caroccia B. et al. Genetic screening in arterial hypertension. Nature Reviews Endocrinology 2017; 13(5): 289-98.
  20. Sousa A.C., Reis R.P., Pereira A. et al. Polimorfismos genéticos associados ao aparecimento de hipertensão arterial numa população portuguesa. Acta Médica Portuguesa 2018; 31(10): 542-50.
  21. Chen X., Qiu C., Kong X. et al. The association between an endothelial nitric oxide synthase gene polymorphism and coronary heart disease in young people and the underlying mechanism. Molecular Medicine Reports 2018; 17(3): 3928-34.
  22. Padma G., Charita B., Swapna N. et al. Novel variants detected in AGT gene among patients with essential hypertension. J. Renin Angiotensin Aldosterone Syst. 2014; 16(3): 642-6.
  23. Hu P.Y., Wang Y.W., Pang X.H. et al. T174M polymorphism in the angiotensinogen gene and risk of myocardial infarction: a meta-analysis. Genet. Mol. Res. 2015; 14(2): 3767-74.
  24. Gunda P., Nagalingam S., Tirunilai P. Role of tagged SNPs of the AGT gene in causing susceptibility to essential hypertension. Clin. Experim. Hypertension 2016; 38(6): 520-5.
  25. Casas J.P., Hingorani A.D., Bautista L.E. et al. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18000 cases and 58000 controls. Arch. Neurol. 2004; 61: 1652-62.
  26. Barouch L.A., Barouch L.A., Harrison R.W. et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 2002; 416: 337-40.
  27. Berger K., Stogbauer F., Stoll M. et al. The glu298asp polymorphism in the nitric oxide synthase 3 gene is associated with the risk of ischemic stroke in two large independent case-control studies. Hum. Genet. 2007; 121: 169-78.
  28. Gooley J.J. Circadian regulation of lipid metabolism. Proc. Nutr. Soc. 2016; 75(4): 440-50.
  29. Yue Y., Liu L., Hu L. et al. The association of lipid metabolism relative gene polymorphisms and ischemic stroke in Han and Uighur population of Xinjiang. J. Lipids in Health and Disease 2017; 16(1): 120.
  30. Voetsch B., Benke K.S., Panhuysen C.l. The combined effect of para-oxonase promoter and coding region polymorphisms on the risk of arterial ischemic stroke among young adults. Arch. Neurol. 2004; 61(3): 351-6.
  31. Пчелина С.Н., Кудинов С.В., Беркович О.А. и др. Ассоциация структурных полиморфизмов промоторной области и кодирующей части гена параоксоназы с развитием инфаркта миокарда у мужчин до 45 лет. Мед. академ. журн. 2003; 2(3): 58-64.
  32. Nielsen A.O., Jensen C.S., Arredouani M.S. et al. Variants of the ADRB2 gene in COPD: systematic review and meta-analyses of disease risk and treatment response. COPD: J. Chron. Obstruc. Pulmon. Dis. 2017; 14(4): 451-60.
  33. Montô F., Oliver E., Vicente D. et al. ß2- and ß1-Adrenoceptor expression exhibits a common regulatory pattern with GRK2 and GRK5 in human and animal models of cardiovascular diseases. J. Cardiovascular Pharm. 2015; 66(5): 478-86.
  34. Vriz O., Minisini R., Citro R. et al. Analysis of beta1 and beta2-adrenergic receptors polymorphism in patients with apical ballooning cardiomyopathy. Acta Cardiol. 2011; 66(6): 787-90.
  35. Xiao P., Shi J., Liu X. Associations of leptin and leptin receptor genetic variants with coronary artery disease: a meta-analysis. Biosci. Rep. 2019; 39(6): BSR20190466.
  36. Nowzari Z., Masoumi M., Nazari-Robati M. et. al. Association of polymorphisms of leptin, leptin receptor and apelin receptor genes with susceptibility to coronary artery disease and hypertension. Life Sciences 2018; 207: 166-71.

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