NEW YORK (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.
The findings implicate variants within the interleukin-2 receptor alpha (IL2RA) gene, the interleukin-7 receptor alpha (IL7RA) gene, and in the HLA-DRA locus.
In 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 parents.
For 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.
Transmission 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 Harvard Medical School in Boston, and colleagues report.
On 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.
"The 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.
In 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.
The IL7RA polymorphism "influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer," the team states.
N Engl J Med 2007;357.
Nat Genet 2007.
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