Tumor necrosis factor alpha-308 alleles in multiple sclerosis and optic neuritis.
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is believed to play an important role in multiple sclerosis (MS) pathogenesis. A bi-allelic polymorphism in the TNF-alpha promoter region (TNF alpha-308), has been reported to influence levels of TNF-alpha production. In the present study, we investigated the TNF alpha-308 polymorphism in 93 patients with MS, 17 patients with optic neuritis (ON) and 95 healthy individuals using an allele-specific PCR technique. Allelic genotype was compared with TNF-alpha mRNA expression levels and HLA class II phenotypes. No significant difference regarding the TNF alpha-308 polymorphism was observed between MS patients and controls. Specifically, the less common allele, TNF2, which is associated with higher expression levels of TNF-alpha, was somewhat less frequent among MS patients. In fact, analysis of 19 patients homozygous for the MS associated HLA-DR-DQ haplotype HLA-Dw2 showed that this haplotype does not carry the TNF2 allele. In addition, in 47 patients, the TNF-alpha alleles did not correlate with expression levels measured as numbers of TNF-alpha expressing cells. Thus, we found no evidence for an important role of TNF alpha-308 polymorphism for genetic susceptibility to MS.
Department of Neurology, Karolinska Institute, Huddinge Hospital, Sweden.
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Navikas
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Lundahl
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Söderström
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Hillert
D000483:Alleles; D001483:Base Sequence; D015870:Gene Expression; D008040:Genetic Linkage; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D009902:Optic Neuritis / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006681:HLA-D Antigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha