" "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), a part of NIH. "This breakthrough was made possible through persistence, an elegant search strategy, and genomic data and techniques that were not available until recently." "

" Both studies involved scanning DNA samples from more than 20,000 MS patients and unaffected individuals in the U.S. and Europe, and looking for single nucleotide polymorphisms (SNPs), which are single-letter variations in a gene's DNA code. Published simultaneously today in the "New England Journal of Medicine" and "Nature Genetics," the studies demonstrate an association between MS and SNPs in two genes that encode interleukin receptors, proteins that serve as antennae on the surface of immune cells. "

" Both studies were supported by NINDS and the National Multiple Sclerosis Society. The "Nature Genetics" study received additional support from the National Institute of General Medical Sciences (NIGMS). The "NEJM" study was also supported by the National Institute of Allergy and Infectious Diseases (NIAID), the National Center for Research Resources (NCRR) and the Penates Foundation. "

" They were conducted by overlapping teams of scientists that used different gene-hunting strategies. One team, which scanned the entire human genome for MS risk factors, was co-led by David Hafler, M.D., Professor of Neurology at Harvard Medical School and Brigham and Women's Hospital in Boston, Stephen Hauser, M.D., Professor and Chair of Neurology at the University of California in San Francisco, and Alastair Compston, FRCP, Ph.D., Head of the Department of Clinical Neurosciences at the University of Cambridge, U.K. The other team, which focused their search on a set of genes they considered potential risk factors for MS, was co-led by Jonathan Haines, Ph.D., Director of the Center for Human Genetics Research at Vanderbilt University Medical Center in Nashville, Tenn. and Margaret A. Pericak-Vance, Ph.D., Director of the Miami Institute for Human Genomics at the University of Miami. Drs. Hauser, Compston, Haines and Pericak-Vance participated in both studies. "

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

" The trigger for MS is unclear, though there's strong evidence for an interplay between genetic susceptibility and some type of environmental factor. Having a relative, especially an identical twin, with MS increases one's risk of developing the disease. In the mid-1970s, researchers discovered that human leukocyte antigens (HLA) account for some of this genetic susceptibility. HLAs are proteins displayed on all the body's cells to help the immune system distinguish self from non-self. A variant of the HLA-DRB1 gene, now widely accepted as the strongest genetic risk factor for MS, increases the likelihood of getting the disease up to four-fold. "

" Still, HLA does not fully explain the genetic basis of MS; scientists have long realized that other genes must play a role that has been difficult to detect. Some studies have pointed to other HLA 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
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