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Interleukin-4 and interleukin-4 receptor gene polymorphisms in inflammatory bowel diseases

Abstract

Imbalances in the regulation of Th1 and Th2 lymphocytes are crucial in inflammatory bowel diseases. Interleukin-4 is secreted by Th2 lymphocytes and downregulates cytokine production from Th1 lymphocytes. Functionally relevant polymorphisms have been described in the interleukin-4 and the interleukin-4 receptor α genes. Association of inflammatory bowel diseases with these polymorphisms has been reported recently suggesting high transcription and enhanced signalling activity in Crohn’s disease. Our study, comprising 211 patients with Crohn’s disease, 147 patients with ulcerative colitis and 446 healthy controls revealed significant association of Crohn’s disease with the −590 T allele of the interleukin-4 gene (P = 0.03). This allele entails reduced expression of IL-4. The reason for these contrasting findings may be discussed in the context of a putatively predisposing allele in linkage disequilibrium with the alleles of the interleukin-4 gene.

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References

  1. Parronchi P, Romagnani P, Annunziato F et al Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn’s disease Am J Pathol 1997 150 823–832

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Monteleone G, Biancone L, Wedel S, Pallone F IL-4 hyporesponsiveness of Crohn’s disease mucosal T lymphocytes: a response of polarised Th1 cells? Dig Liver Dis 2000 32 495–497

    Article  CAS  Google Scholar 

  3. Niessner M, Volk BA 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 1995 101 428–435

    Article  CAS  Google Scholar 

  4. Strober W, Ludviksson BR, Fuss IJ The pathogenesis of mucosal inflammation in murine models of inflammatory bowel disease and Crohn disease Ann Intern Med 1998 128 848–856

    Article  CAS  Google Scholar 

  5. Kambayashi T, Jacob CO, Strassmann G IL-4 and IL-13 modulate IL-10 release in endotoxin-stimulated murine peritoneal mononuclear phagocytes Cell Immunol 1996 171 153–158

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Rioux JD, Silverberg MS, Daly MJ et al Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci Am J Hum Genet 2000 66 1863–1870

    Article  CAS  Google Scholar 

  8. Russel MG, Pastoor CJ, Janssen KM et al Familial aggregation of inflammatory bowel disease: a population-based study in South Limburg, The Netherlands. The South Limburg IBD Study Group Scand J Gastroenterol Suppl 1997 223 88–91

    CAS  PubMed  Google Scholar 

  9. Rosenwasser LJ, Klemm DJ, Dresback JK et al Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy Clin Exp Allergy 1995 25 (Suppl 2) 74–78

    Article  Google Scholar 

  10. Rosenwasser LJ, Borish L Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies (IL-4 and IL-10) Am J Respir Crit Care Med 1997 156 152–155

    Article  Google Scholar 

  11. Kawashima T, Noguchi E, Arinami T et al Linkage and association of an interleukin 4 gene polymorphism with atopic dermatitis in Japanese families J Med Genet 1998 35 502–504

    Article  CAS  Google Scholar 

  12. Mitsuyasu H, Izuhara K, Mao XQ et al Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma Nat Genet 1998 19 119–120

    Article  CAS  Google Scholar 

  13. Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor N Engl J Med 1997 337 1720–1725

    Article  CAS  Google Scholar 

  14. Epplen C, Jaeckel S, Santos E et al Genetic predisposition to Multiple Sclerosis as revealed by immunoprinting Ann Neurol 1997 41 341–352

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Olavesen MG, Hampe J, Mirza MM et al Analysis of single-nucleotide polymorphisms in the interleukin-4 receptor gene for association with inflammatory bowel disease Immunogenetics 2000 51 1–7

    Article  CAS  Google Scholar 

  17. Aithal GP, Day CP, Leathart J, Hudson M Association of single nucleotide polymorphisms in the interleukin-4 gene and interleukin-4 receptor gene with Crohn’s disease in a British population Genes Immun 2001 2 44–47

    Article  CAS  Google Scholar 

  18. Takabayashi A, Ihara K, Sasaki Y, Kusuhara K, Nishima S, Hara T Novel polymorphism in the 5′-untranslated region of the interleukin-4 gene J Hum Genet 1999 44 352–353

    Article  CAS  Google Scholar 

  19. Hijazi Z, Haider MZ Interleukin-4 gene promoter polymorphism [C590T] and asthma in Kuwaiti Arabs Int Arch Allergy Immunol 2000 122 190–194

    Article  CAS  Google Scholar 

  20. Jaeckel S, Epplen JT, Kauth M, Miterski B, Tschentscher F, Epplen C Polymerase chain reaction-single strand conformation polymorphism or how to detect reliably and efficiently each sequence variation in many samples and many genes Electrophoresis 1998 19 3055–3061

    Article  CAS  Google Scholar 

Download references

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Correspondence to W Klein.

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Klein, W., Tromm, A., Griga, T. et al. Interleukin-4 and interleukin-4 receptor gene polymorphisms in inflammatory bowel diseases . Genes Immun 2, 287–289 (2001). https://doi.org/10.1038/sj.gene.6363779

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  • DOI: https://doi.org/10.1038/sj.gene.6363779

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