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Inhibitors in the NFκB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations

Genes & Immunity volume 3, pages 211–219 (2002)Cite this article

Abstract

Multiple sclerosis (MS) is an autoimmune disease displaying different clinical courses. In this multifactorial disease complex environmental as well as genetic predisposition factors contribute to the disease manifestation. Following the candidate gene approach we analysed several genes of the NFκB cascade, which are prime candidates for MS because of their involvement in almost all immunological reactions. MS association was excluded for the NFKB1 and NFKB3 genes, which show remarkably low degrees of polymorphism. The genes of NFκB inhibitors exhibit more sequence variations. In the IKBL gene a predisposing allele was identified (13.1% vs 7.5% in the control group, P < 0.001). This difference in the allelic distribution was even increased in the group of MS patients with a relapsing remitting course of the disease (14.9%, P < 0.0001). A protecting allele was found in the NFKBIA promotor for the patients with primary progressive MS (15.4% vs 28.4% in the control group, P < 0.01). Given predisposing alleles increase MS risk dramatically in certain combinations.

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Acknowledgements

We would like to thank the MS patients for participating in this study and G Rodepeter, G Schlueter, A Kalt, S Schiwy, J Schmitz and T Vollmerhausen for excellent technical assistance.

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Author notes

  1. S Böhringer: Stefan Böhringer is supported by the Vogelsang foundation.

Authors and Affiliations

  1. Department of Molecular Human Genetics, Ruhr-University, Bochum, 44780, Germany

    B Miterski, S Böhringer, W Klein & J T Epplen

  2. Department of Neurology, Kliniken Bergmannsheil, Bochum, Germany

    E Sindern

  3. Department of Neurology, Knappschaftskrankenhaus, Bochum, Germany

    M Haupts

  4. Department of Neurology, St. Josef-Hospital, Ruhr-University, Bochum, Germany

    S Schimrigk

Authors
  1. B Miterski
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  2. S Böhringer
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  4. E Sindern
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  5. M Haupts
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  6. S Schimrigk
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  7. J T Epplen
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Corresponding author

Correspondence to J T Epplen.

Additional information

This work was supported by BMBF (01GG9841)

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Miterski, B., Böhringer, S., Klein, W. et al. Inhibitors in the NFκB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Genes Immun 3, 211–219 (2002). https://doi.org/10.1038/sj.gene.6363846

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  • DOI: https://doi.org/10.1038/sj.gene.6363846

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