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Genes implicated in multiple sclerosis pathogenesis fromconsilience of genotyping and expression profiles in relapse and remission

journal contribution
posted on 2023-05-16, 22:20 authored by Arthur, AT, Armati, PJ, Bye, C, Kilpatrick, TJ, Simon James FooteSimon James Foote, Butzkueven, H, Bruce TaylorBruce Taylor, Tubridy, N, Marriott, M, Chapman, C, Bahlo, M, Speed, TP, Jim Stankovich, Heard, RNS, Stewart, GJ, Pollard, JD, Booth, DR
Background: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Although the pathogenesis of MS remains unknown, it is widely regarded as an autoimmune disease mediated by T-lymphocytes directed against myelin proteins and/or other oligodendrocyte epitopes. Methods: In this study we investigated the gene expression profiles of peripheral blood cells from patients with RRMS during the relapse and the remission phases utilizing gene microarray technology. Dysregulated genes encoded in regions associated with MS susceptibility from genomic screens or previous trancriptomic studies were identified. The proximal promoter region polymorphisms of two genes were tested for association with disease and expression level. Results: Distinct sets of dysregulated genes during the relapse and remission phases were identified including genes involved in apoptosis and inflammation. Three of these dysregulated genes have been previously implicated with MS susceptibility in genomic screens: TGFβ1, CD58 and DBC1. TGFβ1 has one common SNP in the proximal promoter: -508 T>C (rs1800469). Genotyping two Australian trio sets (total 620 families) found a trend for over-transmission of the T allele in MS in females (p < 0.13). Upregulation of CD58 and DBC1 in remission is consistent with their putative roles in promoting regulatory T cells and reducing cell proliferation, respectively. A fourth gene, ALOX5, is consistently found over-expressed in MS. Two common genetic variants were confirmed in the ALOX5 putatve promoter: -557 T>C (rs12762303) and a 6 bp tandem repeat polymorphism (GGGCGG) between position -147 and -176; but no evidence for transmission distortion found. Conclusion: The dysregulation of these genes tags their metabolic pathways for further investigation for potential therapeutic intervention. © 2008 Arthur et al; licensee BioMed Central Ltd.


Publication title

BMC Medical Genetics




Mar 19






Menzies Institute for Medical Research


BioMed Central Ltd

Place of publication

United Kingdom

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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