role of iron metabolism in the severity of MS

Discussion in 'Health and medical' started by Doe, Mar 12, 2004.

  1. Doe

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    Hum Genet. 2004 Mar 11 [Epub ahead of print] Links

    Extended haplotype analysis in the HLA complex reveals an
    increased frequency of the HFE-C282Y mutation in individuals
    with multiple sclerosis.

    Rubio JP, Bahlo M, Tubridy N, Stankovich J, Burfoot R,
    Butzkueven H, Chapman C, Johnson L, Marriott M, Mraz G, Tait
    B, Wilkinson C, Taylor B, Speed TP, Foote SJ, Kilpatrick TJ.

    Walter and Eliza Hall Institute of Medical Research, 3050,
    Parkville, Victoria, Australia.

    In order to resolve a multiple sclerosis (MS) susceptibility
    locus that we had identified in earlier work at the
    telomeric end of the HLA complex, we genotyped another 34
    microsatellite markers (47 in total) across the class
    I/extended class I region in 166 Tasmanian MS case and 104
    control families (D6S299-D6S265). Extended MS
    susceptibility haplotypes, up to 9 Mb in length, were
    observed in 11% of MS cases and 4% of controls. Direct
    comparison of the telomerically extended portion of the MS
    susceptibility haplotype in HFE-Cys282Tyr (C282Y)-
    homozygous haemochromatosis patients identified a common
    ancestry for this genomic segment, which translated into
    an increased frequency of the C282Y allele in 489 MS cases
    from Tasmania and Victoria (10.2%) compared with controls
    (6.7%). Six C282Y homozygotes (1.2%), a three-fold
    increased rate over the general population, and 88
    heterozygotes (18%) were identified. One C282Y-homozygous
    female was identified who had MS and was being treated for
    symptoms of iron overload. Interestingly, for 71 Victorian
    MS cases not of north western European (NWE) ancestry, a
    DR15-independent reduction in the frequency of the C282Y
    allele was observed, supporting the theory of a NWE origin
    for the C282Y-variant of the DR15 ancestral haplotype (C282Y-HLA-A*0301-B*0702-DRB1*1501-
    DQB1*0602). The results of linkage disequilibrium (LD) and
    log linear modelling analyses suggest that C282Y is
    increased in MS cases of NWE ancestry because it is in LD
    with the ancestral DR15 susceptibility haplotype (7.1) and
    that it does not play an independent role in
    predisposition to MS. However, our findings provide the
    impetus for further investigations into the role of iron
    metabolism in the severity of MS.

    PMID: 15014978 [PubMed - as supplied by publisher]


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