THE POLYMORPHISM -308 G/A OF THE TNF GENE AND METABOLIC IMBALANCE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE, TAKING INTO ACCOUNT CARDIOVASCULAR COMPLICATIONS

Authors

  • Tyzhnenko T. V. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine; V. N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0003-1223-6240
  • Misiura K. V. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine» https://orcid.org/0000-0002-0258-9109
  • Kravchun N. O. Multidisciplinary Medical Center “Life Park”; Kharkiv National Medical University, Kharkiv, Ukraine https://orcid.org/0000-0001-7222-8424
  • Gorshunska M. Yu. V.N. Karazin Kharkiv National University, Kharkiv, Ukraine https://orcid.org/0000-0002-4402-9441
  • Pochernyaev A. K. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine; Poltava Scientific Research Forensic Center of the Ministry of Internal Affairs of Ukraine, Poltava, Ukraine https://orcid.org/0000-0001-9520-4492
  • Krasova N. S. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine https://orcid.org/0000-0002-7113-7616
  • Gladkih O. I. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine
  • Leshchenko Zh. A. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine https://orcid.org/0000-0002-6141-689X
  • Fedorova G. V. University of South Bohemia in České Budějovice, Vodňany, Czech Republic https://orcid.org/0000-0001-5492-7459
  • Plohotnichenko O. O. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine
  • Hromakovska O. V. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine
  • Kolesnikova A. O. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine https://orcid.org/0000-0002-3799-0402
  • Jansen E. National Institute for Public Health and the Environment, Bilthoven, The Netherlands
  • Karachentsev Yu. I. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine https://orcid.org/0000-0003-1317-6999
  • Poltorak V. V. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv, Ukraine https://orcid.org/0000-0002-3717-4413

DOI:

https://doi.org/10.21856/j-PEP.2023.2.05

Keywords:

type 2 diabetes mellitus, TNF-α, single nucleotide polymorphism, non-alcoholic fatty liver disease, cardiovascular complications

Abstract

Non-alcoholic fatty liver disease (NAFLD), the most common form of liver disease, is now recognized as a major public health problem worldwide. Tumor necrosis factor alfa (TNF-α), a member of the TNF/TNFR cytokine family, is an intercellular transmission molecule that has been reported in a wide range of human noninfection diseases. The aim of the study was to determine the circulating levels of TNF-α and the nature of its relationships with the components of insulin resistance, both metabolic and hormonal, in patients with type 2 diabetes; and establishing the nature of cardiovascular complications (taking into account TNF-α gene polymorphism) in the presence and absence of NAFLD.

Materials and methods. Case-control study included information about 50 practically healthy people from the city of Kharkiv and the region. The examined population (except control subjects) consisted exclusively of patients with type 2 diabetes mellitus with a long-term existence of the disease against the background of metabolic syndrome, with varying degrees of glycemic control and violations of liver homeostasis in the absence of renal failure. 117 people were selected for analysis: 63 of them with type 2 diabetes in the presence of NAFLD and 54 patients with type 2 diabetes without NAFLD. Genotyping for single nucleotide polymorphism -308 G>A of the TNF-α was performed by the method of polymerase chain reaction with appropriate primers and NcoI endonuclease. Testing of statistical hypotheses was carried out using the odds ratio and χ2 criteria at the significance level of P≤0.05.

Results. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G>A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus.

No association of the studied polymorphism with the risk of developing NAFLD was found. The obtained data make it possible to assume that the studied polymorphism -308 G>A of the TNFα gene is more associated with the risk of developing type 2 diabetes, and the occurrence or progression of NAFLD primarily depends on metabolic imbalance, and not on the contribution of the studied polymorphism.

Conclusions. Non-alcoholic fatty liver disease is closely related to hormonal and metabolic risk factors and markers of cardiovascular disease and type 2 diabetes and may increase the risk of developing and progressing cardiovascular complications. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G>A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus.

References

Younossi Z, Anstee QM, Marietti M, et al. Nat Rev Gastroenterol Hepatol 2018;15: 11-20. https://doi.org/10.1038/nrgastro.2017.109

Browning JD, Szczepaniak LS, Dobbins R, et al. Hepatology 2004;40(6): 1387-1395. https://doi.org/10.1002/hep.20466

Chitturi S, Wong VW, Farrell G. J Gastroenterol Hepatol 2011;26(S1): 163-172. https://doi.org/10.1111/j.1440-1746.2010.06548.x

Abangah G, Yousefi A, Asadollahi R, et al. Iran Red Cres Med J 2014;16(1) e126691-8. https://doi.org/10.5812/ircmj.12669

Jafarian A, Ebrahimi A, Azmoudeh AF, et al. Hepat Mon 2014;14(10): e21574. https://doi.org/10.5812/hepatmon.21574

Lazarus JV, Mark HE, Anstee QM, et al. Nat Rev Gastroenterol Hepatol 2022;19: 60-78. https://doi.org/10.1038/s41575-021-00523-4

Pouwels S, Sakran N, Graham Y, et al. BMC Endocr Disord 2022;22: 63. https://doi.org/10.1186/s12902-022-00980-1

Laxmi MV, Mouen K, Naga Ch. Curr Gastroenterol Reports 2009;11: 50-55. https://doi.org/10.1007/s11894-009-0008-4

Schwimmer JB, Pardee PE, Lavine JE, et al. Circulation 2008;118(3): 277-283. https://doi.org/10.1161/CIRCULATIONAHA.107.739920

Duell BP, Welty FK, Miller M, et al. Arterioscl Thromb Vasc Biol 2022;42: e168-e185. https://doi.org/10.1161/ATV.0000000000000153

Motamed N, Ajdarkosh H, Ahmadi M, et al. World J Hepatol 2020;12(6): 323-331. https://doi.org/10.4254/wjh.v12.i6.323

Gastaldelli A, Kozakova M, Hojlund K, et al. Hepatology 2009;49: 1537-1544. https://doi.org/10.1002/hep.22845

Tana C, Ballestri S, Ricci F, et al. Int J Environ Res Public Health 2019;26;16(17): 3104. https://doi.org/10.3390/ijerph16173104

Akhtar DH, Iqbal U, Vazquez-Montesino LM, et al. J Clin Transl Hepatol 2019;7(4): 362-370. https://doi.org/10.14218/JCTH.2019.00028

Aller R, de Luis DA, Izaola O, et al. Ann Hepatol 2010;9(4): 439-444. https://doi.org/10.1016/S1665-2681(19)31620-5

Wilson AG, Symons JA, McDowell TL, et al. Proc Natl Acad Sci USA 1997;94: 3195-3199. https://doi.org/10.1073/pnas.94.7.3195

El-Tahan RR, Ghoneim AM, El-Mashad N. Springerplus 2016;5(1): 1508. https://doi.org/10.1186/s40064-016-3197-y

Louis E, Franchimont D, Piron A, et al. Clin Exp Immunol 1998;113: 401-406. https://doi.org/10.1046/j.1365-2249.1998.00662.x

Kroeger KM, Steer JH, Joyce DA, Abraham LJ. Cytokine 2000;12: 110-119. https://doi.org/10.1006/cyto.1999.0529

Chalasani N, Younossi Z, Lavine JE, et al. Hepatology 2012;55(6): 2005-2023. https://doi.org/10.1002/hep.25762

Armitage P, Berry G. Statistical methods in medical research. 4rd ed., Blackwell Scientific Publications, 2001: 826 p.

Joffe YT, van der Merwe L, Carstens M, et al. J Nutr 2010;140: 901-907. https://doi.org/10.3945/jn.109.109355

Fernandez-Real JM, Gutierrez C, Ricart W, et al. Diabetes 1997;46: 1468-1472. https://doi.org/10.2337/diab.46.9.1468

Kuffner T, Whitworth W, Jairam M, McNicholl J. Hum Immunol 2003;64: 639-647. https://doi.org/10.1016/s0198-8859(03)00056-9

Abdolmohammadi R, Bonyad M. J Korean Med Sci 2017;32: 33-37. https://doi.org/10.3346/ jkms.2017.32.1.33

Bhushan B, Guleria R, Misra A, et al. Respir Med 2009;103: 386-392. https://doi.org/10.1016/j.rmed.2008.10.001

Karachencev JuІ, Poltorak VV, Kravchun NO, et al. Probl Endokrin Patol 2018;63(1): 29-41. https://doi.org/10.21856/j-PEP.2018.1.04

Golshani H, Haghani K, Dousti M, Bakhtiyari S. Osong Public Health Res Perspect 2015;6(2): 94-99. ttps://doi.org/10.1016/j.phrp.2015.01.003

Dhamodharan U, Viswanathan V, Krishnamoorthy E, et al. Gene 2015;565(1): 62-67. https://doi.org/10.1016/j.gene.2015.03.063

Sesti LEC, Crispim D, Canani LH, et al. Invest Ophthalmol Vis Sci 2015;56(2):1184-1190. https://doi.org/10.1167/iovs.14-15758

Temesszentandrasi G, Voros K, Borocz Z, et al. J Investig Med 2015;63(3): 548-553. https://doi.org/10.1097/JIM.000000000000015

Garcia-Elorriaga G, Mendoza-Aguilar M, del Rey-Pineda G, Gonzalez-Bonilla C. Rev Med Inst Mex Seguro Soc 2013; 51(1): 42-49.

Ferguson D, Finck BN. Nat Rev Endocrinol 2021;(8): 484-495. https://doi.org/10.1038/s41574-021-00507-z

Ciardullo S, Monti T, Sala I, et al. Hypertension 2020;76: 562-568. https://doi.org/10.1161/HYPERTENSIONAHA.120.15220

Houghton D, Zalewski P, Hallsworth K, et al. J Hepatology 2019;70(6): 1203-1213. https://doi.org/10.1016/j.jhep.2019.01.035

Salvi P, Ruffini R, Agnoletti D, et al. J Hypertens 2010;28: 1699-1707. https://doi.org/10.1097/HJH.0b013e32833a7de6

Wong VW, Wong GL-H, Yip GW-K, et al. Gut 2011;60(12): 1721-1727. http://dx.doi.org/10.1136/gut.2011.242016

Chen J, Talwalkar JA, et al. Radiology 2011;259(3): 749-756 https://doi.org/10.1148/radiol.11101942

Huang DQ, Downes M, Evans RM, et al. Semin Liver Dis 2022;42(4): 455-464. https://doi.org/10.1055/a-1930-6658

Targher G, Byrne CD, Tilg H. Gut 2020;69(9): 1-15. https://doi.org/10.1136/gutjnl-2020-320622

Cho HC, Yu G, Lee MY, et al. Cytokine 2013;62(1): 104-109. https://doi.org/10.1016/j.cyto.2013.02.008

Vendrell J, Fernandez-Real JM, Gutierrez C, et al. Atherosclerosis 2003;167(2): 257-264. https://doi.org/10.1016/s0021-9150(02)00429-x

Keso T, Perola M, Laippala P, et al. Atherosclerosis 2001;154(3): 691-697. https://doi.org/10.1016/s0021-9150(00)00602-x

Botkin JR, Teutsch SM, Kaye CI, et al. Genet Med 2010;12: 228-235. https://doi.org/10.1097/GIM.0b013e3181cdde04

Published

2023-06-14

How to Cite

Tyzhnenko, T., Misiura, K., Kravchun, N., Gorshunska, M., Pochernyaev, A., Krasova, N., … Poltorak, V. (2023). THE POLYMORPHISM -308 G/A OF THE TNF GENE AND METABOLIC IMBALANCE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE, TAKING INTO ACCOUNT CARDIOVASCULAR COMPLICATIONS . Problems of Endocrine Pathology, 80(2), 38–49. https://doi.org/10.21856/j-PEP.2023.2.05

Issue

Section

CLINICAL ENDOCRINOLOGY

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