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Definition of polymorphisms and haplotypes in the interleukin-12B gene: association with IL-12 production but not with Crohn's disease

Genes & Immunity volume 5, pages 675–677 (2004)Cite this article

Abstract

Interleukin-12 (IL-12) is a key cytokine for the induction of Th1 immune responses. Recently, functional polymorphisms in IL-12p40 (IL12B) were found to be associated with susceptibility to several autoimmune diseases. Similarly, variation in IL12B might be involved in susceptibility to Crohn's disease (CD), a chronic inflammatory bowel disorder associated with high IL-12 expression. We searched for additional polymorphism in IL12B and genotyped a large cohort of CD patients. Differential in vitro secretors of IL-12 were tested for polymorphism. Polymorphisms were analyzed using the intrafamilial transmission disequilibrium test (TDT) and by case–control analysis. A novel polymorphism was strongly associated with differential expression of IL-12. However, no association with susceptibility to CD was seen for this and other polymorphisms. The high level of conservation is consistent with the key regulatory role of IL-12. The lack of association with IL12B makes it unlikely that this gene is directly involved in the susceptibility to CD.

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References

  1. Trinchieri G, Pflanz S, Kastelein RA . The IL-12 family of heterodimeric cytokines. New players in the regulation of T cell responses. Immunity 2003; 19: 641–644.

    Article  CAS  Google Scholar 

  2. Trinchieri G . Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003; 3: 133–146.

    Article  CAS  Google Scholar 

  3. Morahan G, Huang D, Ymer SI et al. Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet 2001; 27: 218–221.

    Article  CAS  Google Scholar 

  4. Morahan G, Huang D, Wu M et al. Association of IL12B promoter polymorphism with severity of atopic and non-atopic asthma in children. Lancet 2002; 360: 455–459.

    Article  CAS  Google Scholar 

  5. Bouma G, Strober W . The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 2003; 3: 521–533.

    Article  CAS  Google Scholar 

  6. Bouma G, Kaushiva A, Strober W . Experimental murine colitis is regulated by two genetic loci, including one on chromosome 11 that regulates IL-12 responses. Gastroenterology 2002; 123: 554–565.

    Article  CAS  Google Scholar 

  7. Seegers D, Zwiers A, Strober W, Pena AS, Bouma G . A TaqI polymorphism in the 3′UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun 2002; 3: 419–423.

    Article  CAS  Google Scholar 

  8. Huang D, Cancilla MR, Morahan G . Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Genes Immun 2000; 1: 515–520.

    Article  CAS  Google Scholar 

  9. Ymer SI, Huang D, Penna G et al. Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains. Genes Immun 2002; 3: 151–157.

    Article  CAS  Google Scholar 

  10. Hampe J, Grebe J, Nikolaus S et al. Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a cohort study. Lancet 2002; 359: 1661–1665.

    Article  CAS  Google Scholar 

  11. Hall MA, McGlinn E, Coakley G D et al. Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. Genes Immun 2000; 1: 219–224.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This investigation received financial support from the CCFA (GB and ASP) and the Competence Network ‘Inflammatory Bowel Disease’ and the National Genome Research network (SS).

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Authors and Affiliations

  1. Laboratory of Immunogenetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

    A Zwiers, D Seegers, R Heijmans, A S Peña & G Bouma

  2. Department of Gastroenterology, University of Kiel, Germany

    A Koch, J Hampe, S Nikolaus & S Schreiber

Authors
  1. A Zwiers
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  2. D Seegers
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  3. R Heijmans
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  4. A Koch
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  5. J Hampe
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  6. S Nikolaus
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  7. A S Peña
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  8. S Schreiber
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  9. G Bouma
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Correspondence to G Bouma.

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Zwiers, A., Seegers, D., Heijmans, R. et al. Definition of polymorphisms and haplotypes in the interleukin-12B gene: association with IL-12 production but not with Crohn's disease. Genes Immun 5, 675–677 (2004). https://doi.org/10.1038/sj.gene.6364131

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  • DOI: https://doi.org/10.1038/sj.gene.6364131

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