Preview

Russian Journal of Occupational Health and Industrial Ecology

Advanced search

The relationship of polymorphisms of the SOD2, NOS3 and SIRT1 genes with hypertension in employees of the converter workshop of the ferrous metallurgy enterprise

https://doi.org/10.31089/1026-9428-2024-64-1-50-56

EDN: szwlch

Abstract

Workers employed in ferrous metallurgy enterprises are affected by various oxidants, which lead to increased formation of free radicals, suppression of the antioxidant system, initiation of oxidative stress and the development of diseases characterized by high blood pressure. In this regard, the identification of polymorphisms of genes encoding enzymes that are associated with the formation and neutralization of free radicals is an important task of personalized medicine.

The study aims to explore the relationship of polymorphisms rs4880 (SOD2), rs1799983 (NOS3) and rs7069102 (SIRT1) with hypertension in workers of the converter workshop.

To conduct the research the authors used data from periodic medical examinations of men aged 30 to 59 years, including 116 employees of the converter shop and 169 representatives of administrative and managerial personnel (comparison group). Subsequently, we divided each group according to the principle of the presence or absence of a diagnosis of "hypertensive heart disease" (I11 according to ICD-10), established or confirmed during a periodic medical examination. DNA was isolated from peripheral blood using the Lumiere kit for the isolation of genomic DNA from whole blood and literal epithelium (Lumiprobe, Russia) in accordance with the manufacturer's instructions. The scientists performed genotyping using the optical PCR system with real-time optical detection QuantStudio 3 (Thermo Fisher, USA) and ready-made commercial sets "SNP-Screen" (Syntol, Russia).

The ratio of the chances of developing hypertension in the personnel of the converter shop was increased in carriers of mutant genotypes of the SOD2 (TT) gene. Also, the values of blood pressure, total cholesterol and glucose levels were higher in carriers of the mutant TT genotype of the SOD2 gene compared with CC/CT, but only in the group of converter shop workers with hypertension. In addition, in the comparison group with hypertension, systolic and diastolic blood pressure significantly differed, the values of which were higher in carriers of the mutant GG genotype of the SIRT1 gene.

Presumably, an excess of superoxide anion in the TT genotype of the SOD2 gene, together with exposure to harmful environmental factors, may contribute to the development of cardiovascular diseases in workers of the converter workshop.

Ethics. The study was approved in accordance with Protocol No. 1 dated 02/26/2021 and the conclusion of the Local Ethics Committee of the Federal Budgetary Institution of Science "Yekaterinburg Medical Scientific Center for the Prevention and Health Protection of Industrial Workers" of Rospotrebnadzor.

Contribution:
Bereza I.A. — research concept and design, data collection and processing, writing the text, the editing;
Shaikhova D.R. — research concept and design, data collection and processing, writing the text, the editing;
Amromina A.M. — research concept and design, data collection and processing, writing the text, the editing;
Polyanina D.D. — data collection and processing;
Gazimova V.G. — data collection and processing, the editing;
Shastin A.S. — data collection and processing, the editing;
Astakhova S.G. — data collection and processing, the editing;
Sutunkova M.P. — research concept and design, the editing;
Gurvich V.B. — research concept and design.

Funding. The study had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 11.12.2023 / Accepted: 17.01.2024 / Published: 12.02.2024

About the Authors

Ivan A. Bereza
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation

The research associate of Molecular Biology and Electron Microscopy Department at the Federal State Budgetary Institution of Scientific Research of Rospotrebnadzor

e-mail: ivan11011994@gmail.com



Daria R. Shaikhova
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


Anna M. Amromina
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


Daria D. Polyanina
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


Venera G. Gazimova
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


Aleksandr S. Shastin
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


Svetlana G. Astakhova
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


Marina P. Sutunkova
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


Vladimir B. Gurvich
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Russian Federation


References

1. Masyagutova L.M., Abdrakhmanova E.R., Gabdulvaleeva E.F., Perminova V.A. Risk of occupational, work-related, and somatic morbidity among metallurgical industries workers. Vestnik Avitsenny. 2021; 23(2): 280–290. https://doi.org/10.25005/2074-0581-2021-23-2-280-290 (in Russian).

2. Chernyshev V.M., Strelchenko O.V., Mingazov I.F. Health of the economically active population the Russian Federation and the Siberian Federal District. Social and economic aspects. ORGZDRAV: Novosti, mneniya, obuchenie. Vestnik VSHOUZ. 2022; 8(2): 57–72. https://doi.org/10.33029/2411-8621-2022-8-2-57-72 (in Russian).

3. Jomova K., Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology. 2011; 283(2–3): 65–87. https://doi.org/10.1016/j.tox.2011.03.001

4. Birukov K.G. Cyclic Stretch, Reactive Oxygen Species, and Vascular Remodeling. Antioxid. Redox Signal. 2009; 11(7): 1651–1667. https://doi.org/10.1089/ars.2008.2390

5. Heiss E.H., Schachner D., Werner E.R., Dirsch V.M. Active NF-E2-related Factor (Nrf2) Contributes to Keep Endothelial NO Synthase (eNOS) in the Coupled State. J. Biol. Chem. 2009; 284(46): 31579–31586. https://doi.org/10.1074/jbc.M109.009175

6. Roth T.L., Nayak D., Atanasijevic T., Koretsky A.P., Latour L.L., McGavern D.B. Transcranial amelioration of inflammation and cell death after brain injury. Nature. 2014; 505(7482): 223–228. https://doi.org/10.1038/nature12808

7. MacMillan-Crow L.A., Crow J.P., Thompson J.A. Peroxynitrite-Mediated Inactivation of Manganese Superoxide Dismutase Involves Nitration and Oxidation of Critical Tyrosine Residues. Biochemistry. 1998; 37(6): 1613–1622. https://doi.org/10.1021/bi971894b

8. Gongora M.C., Harrison D.G. Sad heart from no SOD. Hypertension. 2008; 51(1): 28–30. https://doi.org/10.1161/HYPERTENSIONAHA.107.101162

9. Harrison D.G., Chen W., Dikalov S., Li L. Regulation of Endothelial Cell Tetrahydrobiopterin. Advances in Pharmacology. 2010; 60: 107–132. https://doi.org/10.1016/B978-0-12-385061-4.00005-2

10. McIntyre M., Bohr D.F., Dominiczak A.F. Endothelial Function in Hypertension: The Role of Superoxide Anion. Hypertension. 1999; 34(4): 539–545. https://doi.org/10.1161/01.HYP.34.4.539

11. Pierdomenico S.D., Di Nicola M., Esposito A.L., Di Mascio R., Ballone E., Lapenna D. et al. Prognostic Value of Different Indices of Blood Pressure Variability in Hypertensive Patients. Am. J. Hypertens. 2009; 22(8): 842–847. https://doi.org/10.1038/ajh.2009.103

12. Holley A.K., Dhar S.K., Xu Y., St. Clair D.K. Manganese superoxide dismutase: beyond life and death. Amino Acids. 2012; 42(1): 139–158. https://doi.org/10.1007/s00726-010-0600-9

13. Landis G.N., Tower J. Superoxide dismutase evolution and life span regulation. Mech. Ageing Dev. 2005; 126(3): 365–379. https://doi.org/10.1016/j.mad.2004.08.012

14. Shimoda-Matsubayashi S., Matsumine H., Kobayashi T., Nakagawa-Hattori Y., Shimizu Y., Mizuno Y. Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson’s disease. Biochem. Biophys. Res. Commun. 1996; 226(2): 561–565. https://doi.org/10.1006/bbrc.1996.1394

15. Sutton A., Imbert A., Igoudjil A., Descatoire V., Cazanave S., Pessayre D., et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet. Genomics. 2005; 15(5): 311–319. https://doi.org/10.1097/01213011-200505000-00006

16. Musunuru K., Kathiresan S. Genetics of Coronary Artery Disease. Annu. Rev. Genomics Hum. Genet. 2010; 11(1): 91–108. https://doi.org/10.1146/annurev-genom-082509-141637

17. Schunkert H., Erdmann J., Samani N.J. Genetics of myocardial infarction: a progress report. Eur. Heart J. 2010; 31(8): 918–925. https://doi.org/10.1093/eurheartj/ehq038

18. Kathiresan S., Srivastava D. Genetics of Human Cardiovascular Disease. Cell. 2012; 148(6): 1242–1257. https://doi.org/10.1016/j.cell.2012.03.001

19. Gazimova V.G., Shastin A.S., Dubenko S.E., Kurbanova N.A., Mazhaeva T.V., Tsepilova T.M., et al. Experience in using the results of periodic medical examinations to assess the risk of developing diseases of the circulatory system. Profil. Meditsina. 2022; 25(5): 61. https://doi.org/10.17116/profmed20222505161 (in Russian).

20. Chebotarev A.G., Sokur O.V., Duryagin I.N. Reduction of occupational health risks for employees of enterprises of mining and metals sector. Metallurg. 2022; (8): 4–9. https://doi.org/10.52351/00260827_2022_08_4 (in Russian).

21. Marsden P.A., Heng H.H., Scherer S.W., Stewart R.J., Hall A.V., Shi X.M. et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J. Biol. Chem. 1993; 268(23): 17478–17488.

22. Rafikov R., Fonseca F.V., Kumar S., Pardo D., Darragh C., Elms S. et al. eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity. J. Endocrinol. 2011; 210(3): 271–284. https://doi.org/10.1530/JOE-11-0083

23. Qian J., Fulton D. Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium. Front. Physiol. 2013; 4: 347. https://doi.org/10.3389/fphys.2013.00347

24. Alcendor R.R., Gao S., Zhai P., Zablocki D., Holle E., Yu X. et al. Sirt1 Regulates Aging and Resistance to Oxidative Stress in the Heart. Circ. Res. 2007; 100(10): 1512–1521. https://doi.org/10.1161/01.RES.0000267723.65696.4a

25. Tanno M., Kuno A., Yano T., Miura T., Hisahara S., Ishikawa S., et al. Induction of Manganese Superoxide Dismutase by Nuclear Translocation and Activation of SIRT1 Promotes Cell Survival in Chronic Heart Failure. J. Biol. Chem. 2010; 285(11): 8375–8382. https://doi.org/10.1074/jbc.M109.090266

26. Chong Z.Z., Wang S., Shang Y.C., Maiese K. Targeting cardiovascular disease with novel SIRT1 pathways. Future Cardiol. 2012; 8(1): 89–100. https://doi.org/10.2217/fca.11.76

27. Chong Z.Z., Shang Y.C., Wang S., Maiese K. SIRT1: new avenues of discovery for disorders of oxidative stress. Expert Opin. Ther. Targets. 2012; 16(2): 167–178. https://doi.org/10.1517/14728222.2012.648926

28. Mattagajasingh I., Kim C.-S., Naqvi A., Yamamori T., Hoffman T.A., Jung S.-B., et al. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc. Natl. Acad. Sci. 2007; 104(37): 14855–14860. https://doi.org/10.1073/pnas.0704329104

29. Kilic U., Gok O., Bacaksiz A., Izmirli M., Elibol-Can B., Uysal O. SIRT1 Gene Polymorphisms Affect the Protein Expression in Cardiovascular Diseases. PLoS ONE. 2014; 9(2): e90428. https://doi.org/10.1371/journal.pone.0090428

30. Kilic U., Gok O., Elibol-Can B., Uysal O., Bacaksiz A. Efficacy of statins on sirtuin 1 and endothelial nitric oxide synthase expression: the role of sirtuin 1 gene variants in human coronary atherosclerosis. Clin. Exp. Pharmacol. Physiol. 2015; 42(4): 321–330. https://doi.org/10.1111/1440-1681.12362


Review

For citations:


Bereza I.A., Shaikhova D.R., Amromina A.M., Polyanina D.D., Gazimova V.G., Shastin A.S., Astakhova S.G., Sutunkova M.P., Gurvich V.B. The relationship of polymorphisms of the SOD2, NOS3 and SIRT1 genes with hypertension in employees of the converter workshop of the ferrous metallurgy enterprise. Russian Journal of Occupational Health and Industrial Ecology. 2024;64(1):50-56. (In Russ.) https://doi.org/10.31089/1026-9428-2024-64-1-50-56. EDN: szwlch

Views: 313


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1026-9428 (Print)
ISSN 2618-8945 (Online)