Abstract
Background
Hashimoto’s thyroiditis (HT), which is also called lymphocytic thyroiditis, is the most frequent autoimmune thyroid disease (AITD), in which T helper-1 lymphocytes mediate the disease. IL-18 is expressed in thyroid follicular cells (TFCs) during HT. The findings of studies aimed at investigating the relationship between IL-18 and HT are highly contradictory. In this study, we aimed to investigate the association between IL-18 gene polymorphisms and HT.
Methods and results
The study included 97 patients diagnosed with HT and 86 volunteers in the healthy control group. The IL18-607C/A (rs1946518) and -137G/C (rs187238) genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. No significant difference in the mean age or sex was observed between the groups (p = 0.763 and p = 0.658, respectively). The -137 IL18 CG genotype was more frequent in HT patients than in controls. In HT patients, the risk of the IL-18 CG genotype was more than 2.237 times higher (OR 2.237%95 Cl 1.195–4.187, p = 0.039) than that of the G/G genotype. Additionally, the -607 AC genotype was more frequent in the control group than in the HT group (in individuals with the IL18 CG genotype).
Conclusions
According to our results, the CG genotype might be a risk factor for HT. Conversely, there is a possibility that the AC genotype plays a protective role against the condition. However, further studies will contribute to new solutions by revealing the molecular and cellular mechanisms of HT.
Similar content being viewed by others
Data availability
The dataset is available from the corresponding author on reasonable request.
References
Cogni G, Chiovato L (2013) An overview of the pathogenesis of thyroid autoimmunity. Hormones 12:19–29. https://doi.org/10.1007/BF03401283
McLeod DS, Cooper DS (2012) The incidence and prevalence of thyroid autoimmunity. Endocrine 42:252–265. https://doi.org/10.1007/s12020-012-9703-2
Antonelli A, Ferrari SM, Corrado A, Domenicantonio AD, Fallahi P (2015) Autoimmune thyroid disorders. Autoimmun Rev 14:174–180. https://doi.org/10.1016/j.autrev.2014.10.016
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002) Serum TSH, T4 and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHALES III). J Clin Endocrin Metab 87:489–499. https://doi.org/10.1210/jcem.87.2.8182
Dong YH, Fu DG (2014) Autoimmune thyroid disease; mechanism. Genetics and current knowledge. Eur Rev Med Pharmacol Sci 18:3611–3618
Pyzik A, Grywalska E, Matuszek BM, Roliński J (2015) Immune disorders in Hashimoto’s thyroiditis: what do we know so far? J Immunol Res 2015:1–8. https://doi.org/10.1155/2015/979167
Charles A, Dinarello MD (1999) IL-18: a TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immunol 103:11–24. https://doi.org/10.1016/s0091-6749(99)70518-x
Gracie JA, Robertson SE, McInnes IB (2003) Interleukin-18. J Leukoc Biol 73:213–224. https://doi.org/10.1189/jlb.0602313
Rothe H, Jenkins NA, Copeland NG, Kolb H (1997) Active stage of autoimmune diabetes is associated with the expression of a novel cytokine, IGIF, which is located near Idd2. J Clin Invest 99:469–474. https://doi.org/10.1172/JCI119181
Pizarro T, Michie M, Bentz M, Woraratanadharm J, Smith MF, Foley E, Moskaluk CA, Bickston SJ, Cominelli F (1999) IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn’s disease: expression and localization in intestinal mucosal cells. J Immunol 162:6829–6835
Tucci M, Quatraro C, Lombardi L, Cecilia P, Dammacco F, Silvetris F (2008) Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: role of interleukin-18. Arthritis Rheum 58:251–262. https://doi.org/10.1002/art.23186
Wildbaum G, Youssef S, Grabie N, Karin N (1998) Neutralizing antibodies to IFN-c-inducing factor prevent experimental autoimmune encephalomyelitis. J Immunol 161:6368–6374
Sakai A, Sugawara Y, Kuroishi T, Sasano T, Sugawara S (2008) Identification of IL18 and Th17 cells in salivary glands of patients with Sjogren’s syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol 181:2898–2906. https://doi.org/10.4049/jimmunol.181.4.2898
Chistiakov DA (2005) Immunogenetics of Hashimoto’s thyroiditis. J Autoimmune Dis 2:1. https://doi.org/10.1186/1740-2557-2-1
Phenekosa C, Vryonidoua A, Gritzapis AD, Baxevanisb CN, Goula M, Papamichail M (2004) Th1 and Th2 serum cytokine profiles characterize patients with Hashimoto’s thyroiditis (Th1) and Graves’ disease (Th2). Neuroimmunomodulation 11:209–213. https://doi.org/10.1159/000078438
Miyauchi S, Matsuura B, Onji M (2000) Increased levels of serum interleukin-18 in Graves’ disease. Thyroid 10:815–819. https://doi.org/10.1089/thy.2000.10.815
Arimitsu J, Hirano T, Higa S, Kawai M, Naka T, Ogata A, Shima Y, Fujimoto M, Yamadori T, Hagiwara K, Ohgawara T, Kubawara Y, Kawase I, Tanaka T (2006) IL-18 gene polymorphisms affect IL-18 production capability by monocytes. Biochem Biophys Res Commun 342:1413–1416. https://doi.org/10.1016/j.bbrc.2006.02.096
Giedraitis V, He B, Huang WX, Hillert J (2001) Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J Neuroimmunol 112:146–152. https://doi.org/10.1016/s0165-5728(00)00407-0
Inoue N, Watanabe M, Nakaguchi A, Ueda D, Kawaguti H, Hidaka Y, Iwatani Y (2017) Functional polymorphisms affecting Th1 differentiation are associated with the severity of autoimmune thyroid diseases. Endocr J 64:695–703. https://doi.org/10.1507/endocrj.EJ16-0551
Mukai T, Hiromatsu Y, Ichimura M, Fukutani T, Kaku H, Myake I, Shoji S, Koda Y, Bednarczuk T (2006) Lack of association of interleukin-18 gene polymorphisms with susceptibility of Japanese populations to Graves’ disease or Graves’ ophthalmopathy. Thyroid 16:243–248. https://doi.org/10.1089/thy.2006.16.243
Ide A, Kawasakı E, Abıru N, Sun F, Fukushıma T, Ishıı R, Takahashi R, Kuwahara H, Fujita N, Atsushi K, Imauzumi M, Oshima K, Usa T, Uotani S, Ejima E, Yamasaki H, Ashizawa K, Yamaguchi Y, Eguchi K (2003) Association of interleukin-18 gene promoter polymorphisms in type 1 diabetes and autoimmune thyroid disease. Ann N Y Acad Sci 1005:436–439. https://doi.org/10.1196/annals.1288.074
Li D, Cai W, Gu R, Zhang Y, Zhang H, Tang K, Xu P, Katirai F, Shi W, Wang L, Huang T, Huang B (2013) Th17 cell plays a role in the pathogenesis of Hashimoto’s thyroiditis in patients. Clin Immunol 149:411–420. https://doi.org/10.1016/j.clim.2013.10.001
Liblau RS, Singer SM, McDevitt HO (1995) Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today 16:34–38. https://doi.org/10.1016/0167-5699(95)80068-9
Huang CY, Ting WH, Lo FS, Wu YL, Chang TY, Chan HW, Lin WS, Chen WF, Lien YP, Lee YJ (2013) The IL18 gene and Hashimoto thyroiditis in children. Hum Immunol 74:120–124. https://doi.org/10.1016/j.humimm.2012.10.005
Umare V, Pradhan V, Nath S, Rajadhyaksha A, Ghosh K, Nadkarni AH (2019) Impact of functional IL-18 polymorphisms on genetic predisposition and diverse clinical manifestations of the disease in Indian SLE patients. Lupus. https://doi.org/10.1177/0961203319834677
Jahanbani-Ardakani H, Alsahebfosoul F, Etemadifar M et al (2019) Interleukin 18 polymorphisms and its serum level in patients with multiple sclerosis. Ann Indian Acad Neurol 22(4):474–476. https://doi.org/10.4103/aian.AIAN_515_18
Wen D, Zhou X-L, Du X, Dong J-Z, Ma C-S (2020) Association of interleukin-18 gene polymorphisms with Takayasu arteritis in a Chinese Han population. Chin Med J. https://doi.org/10.1097/CM9.0000000000001047
Celik SD, Ates O (2018) Genetic analysis of interleukin 18 gene polymorphisms in alopecia areata. J Clin Lab Anal 32:e22386. https://doi.org/10.1002/jcla.22386
Funding
None.
Author information
Authors and Affiliations
Contributions
DK and SKC designed the research. DK and TA performed the research. SKC, GCG and TA analysed the data. TB and AD supervised the research. DK, SKC, TB and AD wrote the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
The research protocol was approved by the ethics committee of Zonguldak Bülent Ecevit university medical school on February 10, 2021 (Reference Number: 2021/03).
Informed consent
Informed consent was obtained all participants.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Karakaya, D., Çakmak Genc, G., Karakas Celik, S. et al. Association between IL-18 gene polymorphisms and Hashimoto thyroiditis. Mol Biol Rep 48, 6703–6708 (2021). https://doi.org/10.1007/s11033-021-06659-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-021-06659-5