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A polymorphism of the NFKBIA gene is associated with Crohn's disease patients lacking a predisposing allele of the CARD15 gene

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Nuclear factor kappa-B (NFκB) plays a crucial role in diseases associated with dysregulated immune response. NFκB inhibitor α downregulates the activity of NFκB.

Patients and methods

To evaluate the contribution of the NFκB inhibitor α gene in Crohn's disease single nucleotide polymorphisms in the 3′-UTR and at position −420 in the promoter were studied in 259 patients with Crohn's disease genotyped for the variations of the CARD15 gene in comparison to 441 healthy controls. Additionally we screened the coding region of the NFκB inhibitor α gene for polymorphisms by SSCP analysis.

Results

In comparison to controls the A allele and the AA genotype frequencies of the single nucleotide polymorphisms in the 3′-UTR were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene. Similarly, the difference between patients harboring no predisposing CARD15 alleles and patients harboring such a variation was significant.

Conclusion

The findings indicate that the phenotype Crohn's disease is to be substructured with respect to genetic susceptibility.

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References

  1. Kmiec Z (1998) Cytokines in inflammatory bowel disease. Arch Immunol Ther Exp (Warsz) 46:143–155

    Google Scholar 

  2. Niessner M, Volk BA (1995) Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction (RT-PCR). Clin Exp Immunol 101:428–435

    CAS  PubMed  Google Scholar 

  3. Russel MG, Pastoor CJ, Janssen KM, van Deursen CT, Muris JW, van Wijlick EH, Stockbrugger RW (1997) Familial aggregation of inflammatory bowel disease: a population-based study in South Limburg, The Netherlands. The South Limburg IBD Study Group. Scand J Gastroenterol 223:88–91

    CAS  Google Scholar 

  4. Hugot JP, Thomas G (1998) Genome-wide scanning in inflammatory bowel diseases. Dig Dis 16:364–369

    CAS  PubMed  Google Scholar 

  5. Hampe J, Cuthbert A, Croucher PJ, Mirza MM, Mascheretti S, Fisher S, Frenzel H, King K, Hasselmeyer A, MacPherson AJ, Bridger S, van Deventer S, Forbes A, Nikolaus S, Lennard-Jones JE, Foelsch UR, Krawczak M, Lewis C, Schreiber S, Mathew CG (2001) Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet 357:1925–1928

    PubMed  Google Scholar 

  6. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J Almer S, Tysk C, O'Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599–603

    PubMed  Google Scholar 

  7. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nunez G, Cho JH (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411:603–606

    PubMed  Google Scholar 

  8. Schreiber S, Nikolaus S, Hampe J (1998) Activation of nuclear factor kappa B inflammatory bowel disease. Gut 42:477–484

    CAS  PubMed  Google Scholar 

  9. Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Scholmerich J, Gross V (1998) Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 15:357–369

    Google Scholar 

  10. Neurath MF, Fuss I, Schurmann G, Pettersson S, Arnold K, Muller-Lobeck H, Strober W, Herfarth C, Buschenfelde KH (1998) Cytokine gene transcription by NF-kappa B family members in patients with inflammatory bowel disease. Ann N Y Acad Sci 859:149–159

    CAS  Google Scholar 

  11. Neurath MF, Pettersson S (1997) Predominant role of NF-kappa B p65 in the pathogenesis of chronic intestinal inflammation. Immunobiology 198:91–98

    CAS  PubMed  Google Scholar 

  12. Ardite E, Panes J, Miranda M, Salas A, Elizalde JI, Sans M, Arce Y, Bordas JM, Fernandez-Checa JC, Pique JM (1998) Effects of steroid treatment on activation of nuclear factor kappaB in patients with inflammatory bowel disease. Br J Pharmacol 124:431–433

    CAS  PubMed  Google Scholar 

  13. Thiele K, Bierhaus A, Autschbach F, Hofmann M, Stremmel W, Thiele H, Ziegler R, Nawroth PP (1999) Cell specific effects of glucocorticoid treatment on the NF-kappaBp65/ IkappaBalpha system in patients with Crohn's disease. Gut 45:693–704

    CAS  PubMed  Google Scholar 

  14. Miterski B, Bohringer S, Klein W, Sindern E, Haupts M, Schimrigk S, Epplen JT (2002) Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Genes Immunol 3:211–219

    CAS  Google Scholar 

  15. Hegazy DM, O'Reilly DA, Yang BM, Hodgkinson AD, Millward BA, Demaine AG (2001) NFkappaB polymorphisms and susceptibility to type 1 diabetes. Genes Immunol 2:304–308

    CAS  Google Scholar 

  16. Duerr RH, Barmada MM, Zhang L, Pfutzer R, Weeks DE (2000) High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11–12. Am J Hum Genet 66:1857–1862

    CAS  PubMed  Google Scholar 

  17. Ma Y, Ohmen JD, Li Z, Bentley LG, McElree C, Pressman S, Targan SR, Fischel-Ghodsian N, Rotter JI, Yang H (1999) A genome-wide search identifies potential new susceptibility loci for Crohn's disease Inflamm Bowel Dis 5:271–278

    Google Scholar 

  18. Glavac D, Ravnik-Glavac M, O'Brien SJ, Dean M (1994) Polymorphisms in the 3' untranslated region of the I kappa B/MAD-3 (NFKBI) gene located on chromosome 14. Hum Genet 93:694–696

    CAS  Google Scholar 

  19. Miterski B, Bohringer S, Klein W, Sindern E, Haupts M, Schimrigk S, Epplen JT (2002) Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Genes Immunol 3:211–219

    CAS  Google Scholar 

  20. Epplen C, Jaeckel S, Santos, D'Souza M Poehlau D, Dorzauer B, Sindern E, Haupts M, Ruede KP, Weber F, Stoever J, Poser S, Gehler W, Malin JP, Przuntek H, Epplen JT (1997) Genetic predisposition to Multiple Sclerosis as revealed by immunoprinting. Ann Neurol 41 341–352

  21. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    PubMed  Google Scholar 

  22. Inoue N, Tamura K, Kinouchi Y, Fukuda Y, Takahashi S, Ogura Y, Inohara N, Nunez G, Kishi Y, Koike Y, Shimosegawa T, Shimoyama T, Hibi T (2002) Lack of common NOD2 variants in Japanese patients with Crohn's disease. Gastroenterology 123:86–91

    CAS  Google Scholar 

  23. Yamazaki K, Takazoe M, Tanaka T, Kazumori T, Nakamura Y (2002) Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with Crohn's disease. J Hum Genet 47:469–472

    CAS  Google Scholar 

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Authors and Affiliations

  1. Abteilung für Humangenetik, Ruhr-Universität, Bochum, Germany

    Wolfram Klein, Michaela Hagedorn, Natascha Duerig & Joerg T. Epplen

  2. Abteilung für Gastroenterologie, Universitätsklinik Bergmannsheil, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Andreas Tromm, Wolff H. Schmiegel & Thomas Griga

  3. Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians Universität, Munich, Germany

    Christian Folwaczny

Authors
  1. Wolfram Klein
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  2. Andreas Tromm
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  3. Christian Folwaczny
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  4. Michaela Hagedorn
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  5. Natascha Duerig
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  6. Joerg T. Epplen
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  7. Wolff H. Schmiegel
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  8. Thomas Griga
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Corresponding author

Correspondence to Thomas Griga.

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Klein, W., Tromm, A., Folwaczny, C. et al. A polymorphism of the NFKBIA gene is associated with Crohn's disease patients lacking a predisposing allele of the CARD15 gene. Int J Colorectal Dis 19, 153–156 (2004). https://doi.org/10.1007/s00384-003-0531-y

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  • DOI: https://doi.org/10.1007/s00384-003-0531-y

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