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Involvement of macrophage migration inhibitory factor gene in celiac disease susceptibility

Genes & Immunity volume 8, pages 168–170 (2007)Cite this article

Abstract

The MIF gene has been associated with several diseases with inflammatory and autoimmune background, such as ulcerative colitis, rheumatoid arthritis and systemic lupus erythematosus. We aimed at testing the influence of two functional MIF promoter variants in celiac disease (CD) susceptibility. A (CAAT)5–8 tetranucleotide repeat at position −794 and a single-nucleotide polymorphism at −173G/C were analyzed in the Spanish population (531 patients and 887 healthy controls). χ2 statistics or Fisher exact test were used for comparisons. The −173C allele significantly increased risk ((CC+GC) vs GG: odds ratio (OR) (95% confidence interval (CI))=1.41 (1.10–1.81); P=0.005), as did carriage of the (CAAT)7 allele (OR (95% CI)=1.36 (1.02–1.82); P=0.03) and of the haplotype (CAAT)7//−173C (OR (95% CI)=1.33 (1.00–1.76); P=0.04). Our data evidence for first time the role of the MIF gene increasing predisposition to CD. A common effect of MIF variants seems to underlie the etiology of these complex conditions.

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References

  1. Sollid LM . Coeliac disease: dissecting a complex inflammatory disorder. Nat Rev Immunol 2002; 2: 647–655.

    Article  CAS  Google Scholar 

  2. Jones RB, Robins GG, Howdle PD . Advances in celiac disease. Curr Opin Gastroenterol 2006; 22: 117–123.

    Article  Google Scholar 

  3. Marsh MN . Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 1992; 102: 330–354.

    Article  CAS  Google Scholar 

  4. Sollid LM, Thorsby E . HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis. Gastroenterology 1993; 105: 910–922.

    Article  CAS  Google Scholar 

  5. Weiser WY, Temple PA, Witek-Giannotti JS, Remold HG, Clark SC, David JR . Molecular cloning of a cDNA encoding a human macrophage migration inhibitory factor. Proc Natl Acad Sci USA 1989; 86: 7522–7526.

    Article  CAS  Google Scholar 

  6. Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W et al. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 1993; 365: 756–759.

    Article  CAS  Google Scholar 

  7. Calandra T, Bernhagen J, Mitchell RA, Bucala R . The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 1994; 179: 1895–1902.

    Article  CAS  Google Scholar 

  8. Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN et al. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma. J Clin Invest 1998; 101: 2869–2874.

    Article  CAS  Google Scholar 

  9. Lan HY, Mu W, Yang N, Meinhardt A, Nikolic-Paterson DJ, Ng YY et al. De Novo renal expression of macrophage migration inhibitory factor during the development of rat crescentic glomerulonephritis. Am J Pathol 1996; 149: 1119–1127.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Donnelly SC, Bucala R . Macrophage migration inhibitory factor: a regulator of glucocorticoid activity with a critical role in inflammatory disease. Mol Med Today 1997; 3: 502–507.

    Article  CAS  Google Scholar 

  11. Renner P, Roger T, Calandra T . Macrophage migration inhibitory factor: gene polymorphisms and susceptibility to inflammatory diseases. Clin Infect Dis 2005; 41 (Suppl 7): S513–S519.

    Article  CAS  Google Scholar 

  12. Paralkar V, Wistow G . Cloning the human gene for macrophage migration inhibitory factor (MIF). Genomics 1994; 19: 48–51.

    Article  CAS  Google Scholar 

  13. Ohkawara T, Nishihira J, Takeda H, Asaka M, Sugiyama T . Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders. J Gastroenterol 2005; 40: 117–122.

    Article  CAS  Google Scholar 

  14. O’Keeffe J, Lynch S, Whelan A, Jackson J, Kennedy NP, Weir DG et al. Flow cytometric measurement of intracellular migration inhibition factor and tumour necrosis factor alpha in the mucosa of patients with coeliac disease. Clin Exp Immunol 2001; 125: 376–382.

    Article  Google Scholar 

  15. Donn RP, Shelley E, Ollier WE, Thomson W . A novel 5′-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2001; 44: 1782–1785.

    Article  CAS  Google Scholar 

  16. Donn R, Alourfi Z, De Benedetti F, Meazza C, Zeggini E, Lunt M et al. Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis. Arthritis Rheum 2002; 46: 2402–2409.

    Article  CAS  Google Scholar 

  17. Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990; 65: 909–911.

  18. Grefte JM, Bouman JG, Grond J, Jansen W, Kleibeuker JH . Slow and incomplete histological and functional recovery in adult gluten sensitive enteropathy. J Clin Pathol 1988; 41: 886–891.

    Article  CAS  Google Scholar 

  19. Kutlu T, Brousse N, Rambaud C, Le Deist F, Schmitz J, Cerf-Bensussan N . Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet. Gut 1993; 34: 208–214.

    Article  CAS  Google Scholar 

  20. Wahab PJ, Meijer JW, Mulder CJ . Histologic follow-up of people with celiac disease on a gluten-free diet: slow and incomplete recovery. Am J Clin Pathol 2002; 118: 459–463.

    Article  Google Scholar 

  21. Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ et al. A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis. Genes Immun 2002; 3: 170–176.

    Article  CAS  Google Scholar 

  22. Hizawa N, Yamaguchi E, Takahashi D, Nishihira J, Nishimura M . Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and atopy. Am J Resp Crit Care Med 2004; 169: 1014–1018.

    Article  Google Scholar 

  23. Donn RP, Plant D, Jury F, Richards HL, Worthington J, Ray DW et al. Macrophage migration inhibitory factor gene polymorphism is associated with psoriasis. J Invest Dermatol 2004; 123: 484–487.

    Article  CAS  Google Scholar 

  24. De Benedetti F, Meazza C, Vivarelli M, Rossi F, Pistorio A, Lamb R et al. Functional and prognostic relevance of the −173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2003; 48: 1398–1407.

    Article  CAS  Google Scholar 

  25. Excoffier L, Slatkin M . Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol 1995; 12: 921–927.

    CAS  Google Scholar 

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Acknowledgements

We thank Carmen Martínez for her skilful technical assistance. All authors declare no competing interests. Elena Urcelay is recipient of a Ramón y Cajal contract of the Spanish Government. Alfonso Martínez is recipient of a research contract of the Spanish Health Ministry (CP04/00175). The Spanish Science and Technology Ministry (MCYT SAF2003-08522 and SAF2003-03460) supported this work. C Núñez received a grant from the afore-mentioned proyect SAF2003-08522.

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  1. C Núñez, B Rueda, J Martín and E Urcelay: These authors contributed equally to this work.

Authors and Affiliations

  1. Servicio de Inmunología Clínica, Hospital Clínico San Carlos, Madrid, Spain

    C Núñez, A Martínez, M Fernández-Arquero, E G de la Concha & E Urcelay

  2. Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain

    B Rueda & J Martín

  3. Servicio de Inmunología, Hospital Virgen de las Nieves, Granada, Spain

    M A López-Nevot

Authors
  1. C Núñez
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  2. B Rueda
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  3. A Martínez
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  4. M A López-Nevot
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  5. M Fernández-Arquero
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  6. E G de la Concha
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  7. J Martín
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Correspondence to E Urcelay.

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Núñez, C., Rueda, B., Martínez, A. et al. Involvement of macrophage migration inhibitory factor gene in celiac disease susceptibility. Genes Immun 8, 168–170 (2007). https://doi.org/10.1038/sj.gene.6364365

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  • DOI: https://doi.org/10.1038/sj.gene.6364365

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