From genotype to protein: how the 308 G/A polymorphism of the TNF-α gene is associated with TNF-α protein levels in patients with Hashimoto’s thyroiditis
DOI:
https://doi.org/10.14739/2310-1210.2025.3.323538Keywords:
Hashimoto thyroiditis, SNP, TNF-α, gene polymorphismAbstract
Aim. To study the 308 G/A polymorphism of the TNF-a gene and its influence on serum levels of TNF-a protein in patients with Hashimoto’s thyroiditis (HT) among the Azerbaijan population.
Materials and methods. The study was conducted at the Department of Biochemistry, Azerbaijan Medical University, between 2021 and 2023. The study enrolled 170 patients diagnosed with HT, and a comparison group consisting of 65 individuals without thyroid pathology or other diseases affecting the immune system. The presence of the TNF-α-308 G/A polymorphism (SNP rs1800629) was determined by the PCR-PDRF method and TNF-α protein serum levels were measured according to the standard ELISA protocol in both groups.
Results. The study on the 308 G/A polymorphism of the TNF-α gene has revealed 49.2 % of patients exhibited the G allele and 55.1 % – the A allele. The AG genotype has been found to be most prevalent in HT patients (57.9 %) being significantly higher than in the comparison group (21.7 % of individuals; p = 0.0006, χ2 = 11.87, OR = 2.85, 95 % CI = 1.55–5.23). Furthermore, serum TNF-α levels have been shown to be significantly higher in HT patients (3.48 ± 1.32 pg/ml) as compared to the control group (2.31 ± 0.74 pg/ml) with statistical significance (p < 0.01).
Conclusions. The most prevalent AG genotype of the TNF-α gene 308 G/A polymorphism has been identified in patients diagnosed with Hashimoto’s thyroiditis. This polymorphism may serve as a genetic marker, indicating a predisposition to autoimmune thyroiditis among the Azerbaijan population. Furthermore, serum TNF-α protein levels have been found to be significantly elevated in patients with Hashimoto’s thyroiditis, which may be associated with the AG genotype of the 308 G/A TNF-α polymorphism.
References
Krupenko SA, Horita DA. The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1. Front Genet. 2019;10:1013. doi: https://doi.org/10.3389/fgene.2019.01013
Tong H, Küken A, Razaghi-Moghadam Z, Nikoloski Z. Characterization of effects of genetic variants via genome-scale metabolic modelling. Cell Mol Life Sci. 2021;78(12):5123-38. doi: https://doi.org/10.1007/s00018-021-03844-4
Chen S, Saeed AF, Liu Q, Jiang Q, Xu H, Xiao GG, et al. Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther. 2023;8(1):207. doi: https://doi.org/10.1038/s41392-023-01452-1
van Loo G, Bertrand MJ. Death by TNF: a road to inflammation. Nat Rev Immunol. 2023;23(5):289-303. doi: https://doi.org/10.1038/s41577-022-00792-3
Poznansky SA, Yu M, Deng K, Fu Q, Markmann JF, LeGuern C. Leveraging the tolerogenic potential of TNF-α and regulatory B cells in organ transplantation. Front Immunol. 2023;14:1173672. doi: https://doi.org/10.3389/fimmu.2023.1173672
Meng X, Layhadi JA, Keane ST, Cartwright NJK, Durham SR, Shamji MH. Immunological mechanisms of tolerance: Central, peripheral and the role of T and B cells. Asia Pac Allergy. 2023;13(4):175-86. doi: https://doi.org/10.5415/apallergy.0000000000000128
Rahimova RR, Efendiyev AM, Shahverdiyeva IJ, Dashdamirova GS, Guliyeva SR, Azizova UH. Study on the role of tissue-specific and non-specific autoantibodies, matrix metalloproteinase-3 and neuron-specific enolase enzymes in the exacerbation of autoimmune thyroiditis. Zaporozhye medical journal. 2024;26(2):118-22. doi: https://doi.org/10.14739/2310-1210.2024.2.296844
Mahdavi Sharif P, Jabbari P, Razi S, Keshavarz-Fathi M, Rezaei N. Importance of TNF-alpha and its alterations in the development of cancers. Cytokine. 2020;130:155066. doi: https://doi.org/10.1016/j.cyto.2020.155066
Zhang N, Wang Q, Tian Y, Xiong S, Li G, Xu L. Expressions of IL-17 and TNF-α in patients with Hashimoto's disease combined with thyroid cancer before and after surgery and their relationship with prognosis. Clin Transl Oncol. 2020;22(8):1280-7. doi: https://doi.org/10.1007/s12094-019-02253-1
Rojas M, Acosta-Ampudia Y, Heuer LS, Zang W, M Monsalve D, Ramírez-Santana C, et al. Antigen-specific T cells and autoimmunity. J Autoimmun. 2024;148:103303. doi: https://doi.org/10.1016/j.jaut.2024.103303
Salomon BL. Insights into the biology and therapeutic implications of TNF and regulatory T cells. Nat Rev Rheumatol. 2021;17(8):487-504. doi: https://doi.org/10.1038/s41584-021-00639-6
Erdogan M, Kulaksizoglu M, Ganidagli S, Berdeli A. Fas/FasL gene polymorphism in patients with Hashimoto's thyroiditis in Turkish population. J Endocrinol Invest. 2017;40(1):77-82. doi: https://doi.org/10.1007/s40618-016-0534-5
Leyane TS, Jere SW, Houreld NN. Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation. Int J Mol Sci. 2022;23(13):7273. doi: https://doi.org/10.3390/ijms23137273
Wenzek C, Boelen A, Westendorf AM, Engel DR, Moeller LC, Führer D. The interplay of thyroid hormones and the immune system - where we stand and why we need to know about it. Eur J Endocrinol. 2022;186(5):R65-R77. doi: https://doi.org/10.1530/EJE-21-1171
Zazeckyte G, Gedvilaite G, Vilkeviciute A, Kriauciuniene L, Balciuniene VJ, Mockute R, et al. Associations of Tumor Necrosis Factor-Alpha Gene Polymorphisms (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), TNF-238A/G (rs361525), and TNF-Alpha Serum Concentration with Age-Related Macular Degeneration. Life (Basel). 2022;12(7):928. doi: https://doi.org/10.3390/life12070928
Khodadadi A, Ghadiri A, Ghafourian M, Iranparast S, Najafian M. The TNF-α-308G/A Gene Polymorphism and Serum TNF-α Levels in Women With Preeclampsia. J Family Reprod Health. 2022;16(3):205-11.
Ghareeb D, Abdelazem AS, Hussein EM, Al-Karamany AS. Association of TNF-α-308 G>A (rs1800629) polymorphism with susceptibility of metabolic syndrome. J Diabetes Metab Disord. 2021;20(1):209-15. doi: https://doi.org/10.1007/s40200-021-00732-3
El-Tahan RR, Ghoneim AM, El-Mashad N. TNF-α gene polymorphisms and expression. Springerplus. 2016;5(1):1508. doi: https://doi.org/10.1186/s40064-016-3197-y
Han SH, Lee NR, Kim HJ, Kang YD, Kim JS, Park JW, et al. Association between the IL-6, IL-10, and TNFα gene polymorphisms and preterm-birth in Korean women. Genes Genomics. 2020;42(7):743-50. doi: https://doi.org/10.1007/s13258-020-00946-4
Gao S, Liang W, Xu T, Xun C, Cao R, Deng Q, et al. Associations of tumor necrosis factor alpha gene polymorphisms and ankylosing spondylitis susceptibility: A meta-analysis based on 35 case-control studies. Immunol Investig. 2021;51(4):859-82. doi: https://doi.org/10.1080/08820139.2021.1882485
Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. Int J Mol Sci. 2021;22(5):2719. doi: https://doi.org/10.3390/ijms22052719
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 R. R. Rahimova, G. Azizova, A. E. Rahimzade, M. Mehdiyev, G. S. Dashdamirova, S. A. Bagirova

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.