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Jul 30, 2007

New Genes Implicated in MS

  • A pair of large-scale genetic studies supported by the NIH revealed two genes that influence the risk of getting multiple sclerosis (MS). Both studies demonstrated an association between MS and SNPs in two genes that encode interleukin receptors, proteins that serve as antennae on the surface of immune cells.

    "These studies describe the first genes conclusively linked to MS in more than 20 years," said Ursula Utz, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS).

    The studies were conducted by overlapping teams of scientists that used different gene-hunting strategies. One team scanned the entire human genome for MS risk factors and was co-led by researchers at Harvard Medical School, Brigham and Women's Hospital, the University of California in San Francisco, and the University of Cambridge. The other team focused their search on a set of genes they considered potential risk factors for MS and was co-led by scientists at  Vanderbilt University Medical Center and the University of Miami.

    Both studies searched for a link between MS and SNPs that were previously identified by the HapMap. In the genome-wide association study, the researchers used gene chip technology to scan more than 500,000 SNPs. In total, they analyzed more than 13,000 DNA samples. 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 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 20–30%.

    The researchers who conducted the candidate gene search also think they know how variation in the IL7R-alpha gene affects the IL7R-alpha protein. They found evidence that the MS-associated variant causes a reduction in the amount of the protein on the surface of T-cells.

    The genome-wide scan also identified nearly a dozen other genes that could represent risk factors for MS, including multiple SNPs in the human leukocyte antigens-DRA locus, previously associated with the disease. Some of the associations were relatively weak, and some of the genes' functions are unclear.

    The research is published simultaneously July 29 in the New England Journal of Medicine and Nature Genetics.



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