Risk Factors for Multiple Sclerosis Identified
Updated: 2007-07-30 12:25:46 -0400 (Reuters Health)
NEWYORK (Reuters Health) – An
international research group has identified several alleles that are associated
with an increased risk of multiple sclerosis, according to a report released
Sunday in The New England Journal of Medicine.
findings implicate variants within the interleukin-2 receptor alpha (IL2RA)
gene, the interleukin-7 receptor alpha (IL7RA) gene, and in the HLA-DRA
the new study, the International Multiple Sclerosis Genetics Consortium used DNA microarray technology to look for
risk alleles in 931 family trios, consisting of an affected child and both
validation, the identified alleles were then examined in another 609 family
trios as well as in 2322 case subjects and 789 controls. Furthermore, to assess
the overall significance and magnitude of the associations uncovered, the
researchers performed a joint analysis of data from 12,360 subjects.
disequilibrium testing of 334,923 single-nucleotide polymorphisms led to the
identification of 110 SNPs possibly linked to multiple sclerosis and that were
submitted for second-stage analysis, lead author Dr. David A. Hafler, from HarvardMedicalSchool in Boston, and colleagues report.
the final analysis, two variants in the IL2RA gene, one in IL7RA gene, and
several in the HLA-DRA locus were strongly linked to multiple sclerosis.
data strongly support the dominance of the HLA locus in the genetic background
of patients with multiple sclerosis but also indicate the involvement of two
interesting genes: IL2RA...and IL7RA, both of which encode proteins
that play a key role in T-cell mediated immunity, Dr. Leena Peltonen, from the
University of Helsinki in Finland, comments in related editorial.
another study, reported in the July 29th advance online issue of Nature
Genetics, Dr. Jonathan L. Haines, from the University of Miami, and colleagues
note an association between the same IL7RA variant and multiple sclerosis.
Their finding is based on an analysis of genotypic data from four independent
family-based or case-control data sets.
influences the amount of soluble and membrane-bound
isoforms of the protein by putatively disrupting an exonic splicing silencer,
the team states.