role of iron metabolism in the severity of MS



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]


Who loves ya. Tom Jesus Was A Vegetarian! Man Is A Herbivore! DEAD