Artigo Acesso aberto Revisado por pares

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

2002; Springer Nature; Volume: 3; Issue: 4 Linguagem: Inglês

10.1038/sj.gene.6363846

ISSN

1476-5470

Autores

Bianca Miterski, Stefan Böhringer, Wolfram Klein, E. Sindern, M. Haupts, Sebastian Schimrigk, Jörg T. Epplen,

Tópico(s)

Cytokine Signaling Pathways and Interactions

Resumo

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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