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

被引:73
作者
Miterski, B
Böhringer, S
Klein, W
Sindern, E
Haupts, M
Schimrigk, S
Epplen, JT [1 ]
机构
[1] Ruhr Univ Bochum, Dept Human Mol Genet, D-44780 Bochum, Germany
[2] Kliniken Bergmannsheil, Dept Neurol, Bochum, Germany
[3] Knappschaftskrankenhaus, Dept Neurol, Bochum, Germany
[4] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, D-4630 Bochum, Germany
关键词
multiple sclerosis; NF kappa B; candidate genes; complex genetics;
D O I
10.1038/sj.gene.6363846
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 NFkappaB 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 NFkappaB 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.
引用
收藏
页码:211 / 219
页数:9
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