August 13, 2007

Genes Linked to Multiple Sclerosis

Cross-section of 2 nerve fibers with thick sheaths In MS, the body's own immune system attacks the protective sheath around nerve fibers, 2 of which are seen here under an electron microscope. Dr. David Furness, Wellcome Images.

A pair of large-scale genetic studies has revealed 2 genes that influence the risk of getting multiple sclerosis (MS). The findings could shed new light on what causes MS and point the way toward potential treatments.

MS is the most common disabling neurological disorder of young adults. It causes limb weakness, vision loss and problems with coordination. It's an autoimmune disease, arising when the body's immune system mistakenly attacks the protective sheath around the delicate cables that nerve cells use to connect with each other. Various drugs can reduce symptoms, but most MS patients become increasingly disabled with time.

The trigger for MS is unclear. Having a relative, especially an identical twin, with MS increases your risk of developing the disease. The first MS susceptibility gene was discovered in the mid-1970s, when researchers found that immune system proteins known as human leukocyte antigens (HLA) account for some of the genetic basis of MS. Still, scientists have long realized that other genes also play a role.

Two large research teams were supported in their search for genes associated with MS by NIH's National Institute of Neurological Disorders and Stroke (NINDS) and the National Multiple Sclerosis Society as well as other NIH institutes. The overlapping teams of scientists used different gene-hunting strategies. One scanned the entire human genome for MS risk factors. The other focused on a set of genes they considered potential risk factors for MS.

The teams together scanned DNA samples from more than 12,000 MS patients and unaffected people in the U.S. and Europe, searching for single-letter DNA variations called single nucleotide polymorphisms (SNPs) associated with MS. The 2 teams published their results simultaneously on July 29, 2007, in the New England Journal of Medicine and Nature Genetics.

Both studies revealed an association between MS and a single SNP in the gene for interleukin 7 receptor-alpha (IL7R-alpha). The genome-wide scan also found 2 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. Both IL2R-alpha and IL7R-alpha have 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%. Although that number might seem small, multiple genetic variations, each carrying a small risk of MS, could combine with each another and with environmental factors to create a large risk.

The genome-wide scan also identified nearly a dozen other genes that could represent risk factors for MS. These results give scientists new ways of looking at the biology of MS and suggest potential new strategies for developing treatments.

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