Skip to main content

Advertisement

Log in

Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

The role of genetic factors in the pathogenesis of Graves’ disease (GD) is not clear. The purpose of this study was to investigate the association between single nucleotide polymorphisms in pro-inflammatory cytokine genes and GD in Iranian patients. A case–control hospital-based study was carried out on 107 GD patients and 140 healthy controls. Cytokine typing was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. The allele and genotype frequencies of the following cytokine genes were determined: TNF-α (−308A/G, −238A/G), IL-2 (−330T/G, +166G/T), IL-6 (−174C/G, A/G nt565), IL-12 (−1188A/C), and IFN-γ (UTR 5644A/T). The following alleles and genotypes were significantly overrepresented in patients: TNF-α −308A allele (P < 0.01) and AA genotype (P < 0.05), IL-2 −330G allele (P < 0.01) and GG genotype (P < 0.01), IL-6 −174C allele (P < 0.01) and CC genotype (P < 0.01), IL-12 −1188C allele (P < 0.01) and CC genotype (P < 0.01), IFN-γ UTR5644T allele (P < 0.01) and TT genotype (P < 0.01). In conclusion, this is the first study to show a significant association between GD and IL-2 −330G, IL-12 −1188C, and IFN-γ UTR 5644T alleles. Our results support the hypothesis that polymorphism in pro-inflammatory cytokines might be involved in predisposition to GD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. A.P. Weetman, N. Engl. J. Med. 343, 1236–1248 (2000)

    Article  CAS  PubMed  Google Scholar 

  2. N. Bougacha-Elleuch, A. Rebai, M. Mnif, H. Makni, M. Bellassouad, J. Jouida, M. Abid, A. Hammadi, J. Autoimmun. 23, 75–80 (2004)

    Article  CAS  PubMed  Google Scholar 

  3. N. Li, Z. Zhou, X. Liu, Y. Liu, J. Zhang, L. Du, M. Wei, X. Chen, Clin. Biochem. 41, 881–886 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. P.J. Hunt, S.E. Marshall, A.P. Weetman, J.I. Bell, J.A. Wass, K.I. Welsh, J. Clin. Endocrinol. Metab. 85, 1984–1988 (2000)

    Article  CAS  PubMed  Google Scholar 

  5. J.M. Heward, A. Allahabadia, J. Daykin, J. Carr-Smith, A. Daly, M. Armitage, P.M. Dodson, M.C. Sheppard, A.H. Barnett, J.A. Franklyn, S.C. Gough, J. Clin. Endocrinol. Metab. 83, 3394–3397 (1998)

    Article  CAS  PubMed  Google Scholar 

  6. H. Ueda, J.M. Howson, L. Esposito, J. Heward, H. Snook, G. Chamberlain, D.B. Rainbow, K.M. Hunter, A.N. Smith, G. Di Genova, M.H. Herr, I. Dahlman, F. Payne, D. Smyth, C. Lowe, R.C. Twells, S. Howlett, B. Healy, S. Nutland, H.E. Rance, V. Everett, L.J. Smink, A.C. Lam, H.J. Cordell, N.M. Walker, C. Bordin, J. Hulme, C. Motzo, F. Cucca, J.F. Hess, M.L. Metzker, J. Rogers, S. Gregory, A. Allahabadia, R. Nithiyananthan, E. Tuomilehto-Wolf, J. Tuomilehto, P. Bingley, K.M. Gillespie, D.E. Undlien, K.S. Ronningen, C. Guja, C. Ionescu-Tirgoviste, D.A. Savage, A.P. Maxwell, D.J. Carson, C.C. Patterson, J.A. Franklyn, D.G. Clayton, L.B. Peterson, L.S. Wicker, J.A. Todd, S.C. Gough, Nature 423, 506–511 (2003)

    Article  CAS  PubMed  Google Scholar 

  7. A. Esteghamati, O. Khalilzadeh, Z. Mobarra, M. Anvari, M. Tahvildari, H.M. Amiri, A. Rashidi, G. Solgi, K. Parivar, B. Nikbin, A. Amirzargar, Eur. J. Intern. Med. 20, 424–428 (2009)

    Article  CAS  PubMed  Google Scholar 

  8. R.H. Chen, W.C. Chen, T.Y. Wang, C.H. Tsai, F.J. Tsai, Int. J. Immunogenet. 32, 343–347 (2005)

    Article  CAS  PubMed  Google Scholar 

  9. A. Balog, J. Gal, Z. Gyulai, S. Zsilak, Y. Mandi, Acta Microbiol. Immunol. Hung. 51, 263–269 (2004)

    Article  CAS  PubMed  Google Scholar 

  10. T. Horiuchi, C. Kiyohara, H. Tsukamoto, T. Sawabe, I. Furugo, S. Yoshizawa, A. Ueda, Y. Tada, T. Nakamura, Y. Kimoto, H. Mitoma, S. Harashima, S. Yoshizawa, T. Shimoda, S. Okamura, K. Nagasawa, M. Harada, Ann. Rheum. Dis. 66, 320–324 (2007)

    Article  CAS  PubMed  Google Scholar 

  11. E. Louis, M. Peeters, D. Franchimont, L. Seidel, F. Fontaine, G. Demolin, F. Croes, P. Dupont, L. Davin, S. Omri, P. Rutgeerts, J. Belaiche, Clin. Exp. Immunol. 119, 64–68 (2000)

    Article  CAS  PubMed  Google Scholar 

  12. R.A. Ajjan, P.F. Watson, A.P. Weetman, Adv. Neuroimmunol. 6, 359–386 (1996)

    Article  CAS  PubMed  Google Scholar 

  13. M. Anvari, O. Khalilzadeh, A. Esteghamati, S.A. Esfahani, A. Rashidi, A. Etemadi, M. Mahmoudi, A.A. Amirzargar, Eye (Lond) (2009) (in press) [Epub ahead of print]

  14. M.Y. Shiau, C.N. Huang, T.P. Yang, Y.C. Hwang, K.J. Tsai, C.J. Chi, Y.H. Chang, Clin. Biochem. 40, 213–217 (2007)

    Article  CAS  PubMed  Google Scholar 

  15. M.J. Simmonds, J.M. Heward, J.M. Howson, H. Foxall, R. Nithiyananthan, J.A. Franklyn, S.C. Gough, Genes Immun. 5, 267–273 (2004)

    Article  CAS  PubMed  Google Scholar 

  16. T. Bednarczuk, Y. Hiromatsu, N. Seki, R. Ploski, T. Fukutani, A. Kurylowicz, K. Jazdzewski, K. Chojnowski, K. Itoh, J. Nauman, Hum. Immunol. 65, 632–639 (2004)

    Article  CAS  PubMed  Google Scholar 

  17. S. Kamizono, Y. Hiromatsu, N. Seki, T. Bednarczuk, H. Matsumoto, A. Kimura, K. Itoh, Clin. Endocrinol. (Oxf) 52, 759–764 (2000)

    Article  CAS  Google Scholar 

  18. J. Nakkuntod, T. Wongsurawat, P. Charoenwongse, T. Snabboon, V. Sridama, N. Hirankarn, Asian Pac. J. Allergy Immunol. 24, 207–211 (2006)

    CAS  PubMed  Google Scholar 

  19. O. Khalilzadeh, M. Anvari, F. Momen-Heravi, A. Esteghamati, A. Rashidi, M. Mahmoudi, B. Nikbin, A. Amirzargar, Clin Exp Med (2009) (in press) [Epub ahead of print]

  20. L. Beretta, F. Cappiello, J.H. Moore, M. Barili, C.S. Greene, R. Scorza, Arthritis Rheum. 59, 974–983 (2008)

    Article  CAS  PubMed  Google Scholar 

  21. D.D. Dao, J.R. Sawyer, J. Epstein, R.G. Hoover, B. Barlogie, G. Tricot, Leukemia 8, 1280–1284 (1994)

    CAS  PubMed  Google Scholar 

  22. D. Fishman, G. Faulds, R. Jeffery, V. Mohamed-Ali, J.S. Yudkin, S. Humphries, P. Woo, J. Clin. Invest. 102, 1369–1376 (1998)

    Article  CAS  PubMed  Google Scholar 

  23. C.M. Chapman, J.P. Beilby, S.E. Humphries, L.J. Palmer, P.L. Thompson, J. Hung, Eur. Heart J. 24, 1494–1499 (2003)

    Article  CAS  PubMed  Google Scholar 

  24. M. Kopf, G. Le Gros, A.J. Coyle, M. Kosco-Vilbois, F. Brombacher, Immunol. Rev. 148, 45–69 (1995)

    Article  CAS  PubMed  Google Scholar 

  25. J.J. Corrales, A. Orfao, A. Lopez, M.T. Mories, J.M. Miralles, J. Ciudad, Cytometry 30, 118–123 (1997)

    Article  CAS  PubMed  Google Scholar 

  26. T. Bednarczuk, A. Kurylowicz, Y. Hiromatsu, J. Kiljanskic, A. Telichowska, J. Nauman, Autoimmunity 37, 223–226 (2004)

    Article  CAS  PubMed  Google Scholar 

  27. Y. Hiromatsu, T. Fukutani, M. Ichimura, T. Mukai, H. Kaku, I. Miyake, K. Yamada, Endocr. J. 53, 753–759 (2006)

    Article  CAS  PubMed  Google Scholar 

  28. Y. Ikeda, W. Yoshida, T. Noguchi, K. Asaba, T. Nishioka, T. Takao, K. Hashimoto, Endocr. J. 51, 609–613 (2004)

    Article  CAS  PubMed  Google Scholar 

  29. I. Dahlman, I.A. Eaves, R. Kosoy, V.A. Morrison, J. Heward, S.C. Gough, A. Allahabadia, J.A. Franklyn, J. Tuomilehto, E. Tuomilehto-Wolf, F. Cucca, C. Guja, C. Ionescu-Tirgoviste, H. Stevens, P. Carr, S. Nutland, P. McKinney, J.P. Shield, W. Wang, H.J. Cordell, N. Walker, J.A. Todd, P. Concannon, Nat. Genet. 30, 149–150 (2002)

    Article  CAS  PubMed  Google Scholar 

  30. T. Fukutani, Y. Hiromatsu, H. Kaku, I. Miyake, T. Mukai, Y. Imamura, S. Kohno, N. Takane, S. Shoji, S. Otabe, K. Yamada, Thyroid 14, 93–97 (2004)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by a grant from the Research Committee of Tehran University of Medical Sciences (TUMS), Tehran, Iran

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aliakbar Amirzargar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anvari, M., Khalilzadeh, O., Esteghamati, A. et al. Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ. Endocr 37, 344–348 (2010). https://doi.org/10.1007/s12020-010-9311-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-010-9311-y

Keywords

Navigation