Skip to main content

Advertisement

Log in

Association of interferon-gamma and tumor necrosis factor alpha polymorphisms with susceptibility to vitiligo in Iranian patients

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Vitiligo is a common skin disorder that is caused by selective destruction of melanocytes, resulting in disfiguring loss of pigment. There are convincing evidences that cytokines and T cell mediated immunity may have a role in its pathogenesis. Given the fact that cytokine production is under genetic control, in this study, we have investigated IFN-γ +874 T/A and TNF-α −308 G/A gene polymorphisms in a total of 176 vitiligo patients and 545 controls. IFN-γ +874 T/A and TNF-α −308 G/A gene polymorphisms were genotyped via Allele Specific Oligonucleotide PCR (ASO-PCR) method. The results showed that the TNF-α −308 G/A polymorphism was more common in vitiligo patients than controls (= 0.0004). This difference was only significant between female patients and controls (P < 0.0001), while there was no significant difference between male patients and male controls (= 0.90). The distribution of IFN-γ genotypes in vitiligo patients did not differ significantly from that in control subjects (P = 0.56). Since the presence of A nucleotide at position −308 of TNF-α gene is associated with increased cytokine production, therefore, the higher frequency of TNF-α −308 A allele in vitiligo patients compared to controls may be considered as a genetic susceptibility factor towards the development of vitiligo.

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. Abdel Naser MB, Krüger-Krasagakes S, Krasagakis K, Gollnick H, Orfanos CE (1994) Further evidence for involvement of both cell mediated and humoral immunity in generalized vitiligo. Pigment Cell Res 7:1–8

    Article  PubMed  CAS  Google Scholar 

  2. Al Badri AM (1993) Abnormal expression of MHC class ll and ICAM-l by melanocytes in vitiligo. J Pathol 169:203–206

    Article  PubMed  CAS  Google Scholar 

  3. Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA (2003) Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 16:208–214

    Article  PubMed  Google Scholar 

  4. Bolognia JL, Pawelek JM (1988) Biology of hyperpigmentation. J Am Acad Dermatol 19:217–255

    Article  PubMed  CAS  Google Scholar 

  5. Caixia T, Hongwen F, Xiran L (1999) Levels of soluble interleukin-2 receptor in the sera and skin tissue fluids of patients with vitiligo. J Dermatol Sci 21:59–62

    Article  PubMed  CAS  Google Scholar 

  6. Carnevale A, Zavala C, Castillo VD, Maldonado RR, Tamayo L (1980) Analisis genetico de 127 families con vitiligo. Rev Invest Clin 32:37–41

    PubMed  CAS  Google Scholar 

  7. Castanet J, Ortonne JP (1997) Pathophysiology of vitiligo. Clin Dermatol 15:845–851

    Article  PubMed  CAS  Google Scholar 

  8. Chevillard C, Henri S, Stefani F, Parzy D, Dessein A (2002) Two new polymorphisms in the human interferon gamma (IFN-gamma) promotor. Eur J Immunogenet 29:53–56

    Article  PubMed  CAS  Google Scholar 

  9. Grimes PE, Morris R, Avaniss-Aghajani E, Soriano T, Meraz M, Metzger A (2004) Topical tacrolimus therapy for vitiligo: therapeutic responses and skin messenger RNA expression of proinflammatory cytokines. J Am Acad Dermatol 51:52–61

    Article  PubMed  Google Scholar 

  10. GrimesPE Wojdani A, Loeb LJ, Franco R, Kelly AP (1992) The effects of isoprinosine treatment on repigmentation and immunologic aberrations in vitiligo. J Invest Dermatol 98:534

    Google Scholar 

  11. Hafez M, Sharaf L, Abd el-Nabi SM (1983) The genetics of vitiligo. Acta Derm Venereol 63:249–251

    PubMed  CAS  Google Scholar 

  12. Hann SK, Park YK, Lee KG, Choi EH, Im S (1992) Epidermal changes in active vitiligo. J Dermatol 19:217–222

    PubMed  CAS  Google Scholar 

  13. Huang CL, Nordlund JJ, Boissy R (2002) Vitiligo. A manifestation of apoptosis. Am J Clin Dermatol 3:301–308

    Article  PubMed  CAS  Google Scholar 

  14. Kovacs SO (1998) Vitiligo. J Am Acad Dermatol 38:647–666

    Article  PubMed  CAS  Google Scholar 

  15. Le Poole IC, Das PK, van den Wijngaard RM, Bos JD, Westerhof W (1993) Review of the etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol 2:145–153

    Article  PubMed  CAS  Google Scholar 

  16. Le Pool IC, van den Wijngaard RM, Westerhof W, Dutrieux R, Das PK (1993) Presence or absence of melanocytes in vitiligo lesions: an immunohistochemical investigation. J Invest Dermatol 100:816–822

    Article  Google Scholar 

  17. Majumder PP (2000) Genetics and prevalence of vitiligo vulgaris. In: Hann S-K, Nordlund JJ (eds) Vitiligo. Blackwell, Oxford, pp 18–20

    Chapter  Google Scholar 

  18. Martinez-Esparza M, Jimenez-Cervantes C, Solano F, Lozano JA, Garcia-Borron JC (1998) Mechanisms of melanogenesis inhibition by tumor necrosis factor-α in B16–F10 mouse melanoma cells. Eur J Biochem 255:139–146

    Article  PubMed  CAS  Google Scholar 

  19. Moellmann G, Klein-Angerer S, Scollay DA, Nordlund JJ, Lerner AB (1982) Extracellular granular material and degeneration of keratinocytes in the normally pigmented epidermis of patients with vitiligo. J Invest Dermatol 97:321–330

    Article  Google Scholar 

  20. Morelli JG, Norris DA (1993) Influence of inflammatory mediators and cytokines on human melanocyte function. J Invest Dermatol 100:191–195

    Article  Google Scholar 

  21. Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabiani M, Fabbri P (2002) New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 15:87–92

    Article  PubMed  CAS  Google Scholar 

  22. Ongenae K, Van Geel N, Naeyaert JM (2003) Evidence for an autoimmune pathogenesis of vitiligo. Pigment Cell Res 16:90–100

    Article  PubMed  Google Scholar 

  23. Ortonne JP, Bose SK (1993) Vitiligo: where do we stand? Pigment Cell Res 6:61–72

    Article  PubMed  CAS  Google Scholar 

  24. Pravica V, Asderakis A, Perrey C, Hajeer A, Sinnott PJ, Hutchison IV (1999) In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene. Eur J Immunogenet 26:1–3

    Article  PubMed  CAS  Google Scholar 

  25. Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV (2000) A single nucleotide polymorphism in the first intron of the human IFN-γ gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-γ production. Hum Immunol 61:863–866

    Article  PubMed  CAS  Google Scholar 

  26. Rubin LA, Nelson DL (1990) The soluble interleukin-2 receptor biology, function, and clinical application. Ann Intern Med 13:619–627

    Google Scholar 

  27. Salzer BA, Schallreuter KU (1995) Investigation of the personality structure in patients with vitiligo and a possible association with impaired catecholamine metabolism. Dermatology 190:109–115

    Article  PubMed  CAS  Google Scholar 

  28. Taneja A, Trehan M, Taylor CR (2003) Pharmacology and therapeutics. 308-nm excimer laser for the treatment of localized vitiligo. Int J Dermatol 42:658–662

    Article  PubMed  Google Scholar 

  29. Verjans GM, Brinkman BM, VanDoornik CE, Kijlstra A, Verweij CL (1994) Polymorphism of tumor necrosis factor-alpha (TNF-alpha) at position −308 in relation to ankylosing spondylitis. Clin Exp Immunol 97:45–47

    PubMed  CAS  Google Scholar 

  30. Wańkowicz-Kalińska A, van den Wijngaard RM, Tigges BJ, Westerhof W, Ogg GS, Cerundolo V, Storkus WJ, Das PK (2003) Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo. Lab Invest 83:683–695

    PubMed  Google Scholar 

  31. Wilson AG, de Giovine FS, Blakemore AL, Duff GW (1992) Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR producy. Hum Mol Gene 5:353

    Article  Google Scholar 

  32. Yazici AC, Erdal ME, Kaya TI, Ikizoglu G, Savasoglu K, Camdeviren H, Tursen U (2006) Lack of association with TNF-alpha −308 promoter polymorphism in patients with vitiligo. Arch Dermatol Res 298:46–49

    Article  PubMed  CAS  Google Scholar 

  33. Yohn JJ, Critelli M, Lyons MB, Norris DA (1990) Modulation of melanocyte intercellular adhesion molecule-1 by immune cytokines. J Invest Dermatol 90:233–237

    Article  Google Scholar 

  34. Zimonjic DB, Rezanka LJ, Evans CH, Polymeropoulos MH, Trent JM, Popescu NC (1995) Mapping of the immune interferon gamma gene (IFNG) to chromosome band 12q14 by flourescence in situ hybridization. Cytogenet Cell Genet 71:247–248

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank Mr. Javad Khishdoost and Marjan Dehghan from Autoimmune Diseases Research Center for their technical assistance. This study was financially supported by a grant from the Shiraz University of Medical Sciences.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eskandar Kamali-Sarvestani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Namian, AM., Shahbaz, S., Salmanpoor, R. et al. Association of interferon-gamma and tumor necrosis factor alpha polymorphisms with susceptibility to vitiligo in Iranian patients. Arch Dermatol Res 301, 21–25 (2009). https://doi.org/10.1007/s00403-008-0904-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-008-0904-8

Keywords

Navigation