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After a decades-long search, scientists identify new genetic risk factors for multiple sclerosis

genes, but neither of the two genes reported today belong to that category. Both genes encode receptors on the surface of T cells the immune system's mobile infantry that enable the cells to respond to regulatory, secreted proteins called interleukins.

"These are the first non-HLA genes to be unequivocally associated with MS," said Dr. Pericak-Vance. "They give us a new way of looking at the biology of the disease, and could be targets for therapeutic development."

Both studies searched for a link between MS and SNPs that were previously identified by the HapMap, an NIH-supported project to catalog genetic differences in human populations.

In the genome-wide association study, the first of its kind in MS, the researchers used gene chip technology to scan more than 500,000 SNPs. In total, they analyzed more than 13,000 DNA samples, many of them collected and stored by the Center for Genetic Studies at the National Institute of Mental Health (NIMH) and the U.K.'s Wellcome Trust Case Control Consortium. In the candidate gene study, the researchers scanned DNA samples from four large groups in the U.S, U.K. and Belgium, totaling more than 10,000 people.

Both studies revealed an association between MS and a single SNP in the gene interleukin 7 receptor-alpha (IL7R-alpha). The genome-wide scan also found two SNPs in the gene for interleukin 2 receptor-alpha (IL2R-alpha) associated with the disease. Both receptors are known to influence the way that T cells patrol the body for pathogens. IL2R-alpha has previously been implicated in other autoimmune diseases, including type 1 diabetes.

Each of the SNPs associated with MS appears to increase the risk of developing the disease by about 20 to 30 percent. Although that number might seem small, "it's the size of effect we expect to see for genes outside of HLA," said Dr. Haines. Multiple genetic variations, each carrying a small risk of MS, could combine with one a
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Contact: Daniel Stimson
stimsond@ninds.nih.gov
301-496-5751
NIH/National Institute of Neurological Disorders and Stroke
29-Jul-2007


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