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The influence of single-nucleotide polymorphisms of interleukin-1β -511 and +3954 on the susceptibility to Hashimoto’s thyroiditis in Egyptian women: immune-endocrine interactions

Abstract

Background

Hashimoto’s thyroiditis (HT) is a T-cell-mediated autoimmune disease. Cytokines play a crucial role in modulating immune responses that affect the balance between maintenance of self-tolerance and initiation of autoimmunity. Thus, we aimed to explore the possible associations of interleukin (IL-1β) –511C/T (rs 16944) and IL-1β +3954C/T (rs1143634) gene polymorphisms with susceptibility of HT, and to clarify the impact of these polymorphisms on thyroid function of Egyptian women.

Patients and methods

Polymorphisms of the IL-1β –511 and IL-1β +3954 genes were assessed in a case–control study comprising 110 HT patients and 90 controls. Genetic variants were genotyped by multiplex PCR. Polymorphisms of the IL-1β were studied by PCR-restriction fragment length polymorphism analysis.

Results

Our results revealed that the IL-1β –511 CT genotype distribution was significantly higher in HT patients than in controls. With regard to IL-1β +3954 gene polymorphisms, our results showed that there was a nonsignificant difference between the control and HT groups. Women carrying TT and CT genotype of IL-1β –511 had significantly higher values of C-reactive protein, thyroid-stimulating hormone, anti-thyroid peroxidase, and anti-thyroglobulin. As regards the IL-1β serum level, women carrying TT and TC genotype of IL-1β –511 had significantly higher values compared with patients carrying the CC genotype. Moreover, anti-thyroglobulin and free thyroxine were the only independently correlated factors with IL-1β serum level by linear regression analysis.

Conclusion

CT genotype distribution was significantly higher in patients with HT than in controls with regard to IL-1β –511 (C>T) gene polymorphisms.

References

  1. Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003; 348:2646–2655.

    Article  Google Scholar 

  2. Ganesh BB, Bhattacharya P, Gopisetty A, Prabhakar BS. Role of cytokines in the pathogenesis and suppression of thyroid autoimmunity. J Interferon Cytokine Res 2011; 31:721–731.

    Article  CAS  Google Scholar 

  3. Kawashima A, Tanigawa K, Akama T, Yoshihara A, Ishii N, Suzuki K. Innate immune activation and thyroid autoimmunity. J Clin Endocrinol Metab 2011; 96:3661–3671.

    Article  CAS  Google Scholar 

  4. Brown KD, Zurawski SM, Mosmann TR, Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol 1989; 142:679–687.

    CAS  PubMed  Google Scholar 

  5. Kim CH. Chemokine-chemokine receptor network in immune cell trafficking. Current Drug Targets 2004; 4:343–361.

    CAS  PubMed  Google Scholar 

  6. Rasmussen AK, Bendtzen K, Feldt-Rasmussen U. Thyrocyte-interleukin-1 interactions. Exp Clin Endocrinol Diabetes 2000; 108:67–71.

    Article  CAS  Google Scholar 

  7. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996; 87:2095–2147.

    Article  CAS  Google Scholar 

  8. García-González MA, Aísa MA, Strunk M, Benito R, Piazuelo E, Jimenez P, Sopena F, Lanas A. Relevance of IL-1 and TNF gene polymorphisms on interleukin-1 beta and tumor necrosis factor-alpha gastric mucosal production. Hum Immunol 2009; 70:935–945.

    Article  Google Scholar 

  9. Stegger JG, Schmidt EB, Tjønneland A, Kopp TI, Sørensen TI, Vogel U, Overvad K. Single nucleotide polymorphisms in IL1B and the risk of acute coronary syndrome: a Danish case-cohort study. PLoS One 2012; 7: e36829.

    Article  CAS  Google Scholar 

  10. Tsai LJ, Hsiao SH, Tsai JJ, Lin CY, Tsai LM, Lan JL. Higher genetic susceptibility to inflammation in mild disease activity of systemic lupus erythematosus. Rheumatol Int 2009; 29:1001–1011.

    Article  CAS  Google Scholar 

  11. Parks CG, Cooper GS, Dooley MA. Systemic lupus erythematosus and genetic variation in the interleukin 1 gene cluster: a population-based study in the southeastern United States. Ann Rheum Dis 2004; 63:91–94.

    Article  CAS  Google Scholar 

  12. Johnsen AK, Plenge RM, Butty V. A broad analysis of IL1 polymorphism and rheumatoid arthritis. Arthritis Rheum 2008; 58:1947–1957.

    Article  CAS  Google Scholar 

  13. Fagiolo E, Vigevani F, Pozzetto U. High cytokine serum levels in patients with autoimmune hemolytic anemia (AIHA). Immunol Invest 1994; 23:449–456.

    Article  CAS  Google Scholar 

  14. Chen RH, Chen WC, Chang CT, Tsai CH, Tsai FJ. Interleukin-1-beta gene, but not the interleukin-1 receptor antagonist gene, is associated with Graves’ disease. J Clin Lab Anal 2005; 19:133–138.

    Article  CAS  Google Scholar 

  15. O’Sullivan BJ, Thomas HE, Pai S, Santamaria P, Iwakura Y, Steptoe RJ, Kay TW, Thomas R. IL-1 beta breaks tolerance through expansion of CD25 + effector T cells. J Immunol 2006; 176:7278–7287.

    Article  Google Scholar 

  16. Effraimidis G, Wiersinga WM. Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol 2014; 170: R241–R252.

    Article  CAS  Google Scholar 

  17. Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, Chatterjee VK, et al. Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype. J Clin Endocrinol Metab 2006; 91:4873–4880.

    Article  CAS  Google Scholar 

  18. Wiersinga WM. Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab 2016; 31:213–222.

    Article  CAS  Google Scholar 

  19. Kristensen B. Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls. Dan Med J 2016; 63: pii:B5177.

    PubMed  Google Scholar 

  20. Khaled TE, Mohamed AM, Mohamed ME, Abd Elmoneim E. Thyroid dysfunction and anti-thyroid antibodies in Egyptian patients with systemic lupus erythematosus: correlation with clinical musculoskeletal manifestations. Egypt Rheumatol 2014; 36:173–178.

    Article  Google Scholar 

  21. Lacka K, Paradowska-Gorycka A, Maciejewski A, Kramer L, Herman WA, Lacki JK. Interleukin 1 beta (IL1beta) gene polymorphisms (SNP-511 and SNP+3953) in Hashimoto’s thyroiditis among the Polish population. Exp Clin Endocrinol Diabetes 2014; 122:544–547.

    Article  CAS  Google Scholar 

  22. Kammoun-Krichen M, Bougacha-Elleuch N, Makni K, Rebai M, Peraldi-Roux S, Rebai A, et al. Association analysis of interleukin-1 gene polymorphisms in autoimmune thyroid diseases in the Tunisian population. Eur Cytokine Netw 2007; 18:196–200.

    CAS  PubMed  Google Scholar 

  23. Hunt PJ, Marshall SE, Weetman AP, Bell JI, Wass JA, Welsh KI. Cytokine gene polymorphisms in autoimmune thyroid disease. J Clin Endocrinol Metab 2000; 85:1984–1988.

    Article  CAS  Google Scholar 

  24. Lacka K, Gasinska T, Gasinska T, Soszynska J, Wichary H, Karmer L, Lacki JK. Interleukin-1β Gene (IL-1β) polymorphisms (SNP –511 and SNP +3953) in thyroid-associated ophthalmopathy (TAO) among the Polish population. Curr Eye Res 2009; 34:215–220.

    Article  CAS  Google Scholar 

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Correspondence to Nearmeen M. Rashad MD.

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Rashad, N.M., Soliman, M.H., Mousa, M.M. et al. The influence of single-nucleotide polymorphisms of interleukin-1β -511 and +3954 on the susceptibility to Hashimoto’s thyroiditis in Egyptian women: immune-endocrine interactions. Egypt J Intern Med 31, 14–21 (2019). https://doi.org/10.4103/ejim.ejim_69_18

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