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Scientists discover genetic marker responsible for two-fold increase in risk of rheumatoid arthritis

MANHASSET, NY A team of researchers has discovered a genetic variation that doubles the risk for rheumatoid arthritis (RA). The variation, referred to as a single nucleotide polymorphism (SNP, pronounced "snip"), is present in about 28 percent of individuals with rheumatoid arthritis and 17 percent of the general population. This discovery resulted from a collaboration between scientists from the North American Rheumatoid Arthritis Consortium (NARAC), led by Peter K. Gregersen, MD, of the North Shore-Long Island Jewish Research Institute in Manhasset, NY, Celera Diagnostics and Genomics Collaborative, Inc. The team's findings are being published in the August 2004 issue of the American Journal of Human Genetics.

"This is an important discovery, really a major genetic variant identified in a U.S. study that clearly seems to be involved in rheumatoid arthritis," said Stephen I. Katz, MD, PhD, director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the lead agency at the National Institutes of Health (NIH) that supports NARAC.

While scientists still do not know the exact cause of RA, they do know it is an autoimmune disease in which the body's natural immune system does not function properly and attacks its own healthy joint tissues. This causes inflammation and subsequent joint damage.

The SNP they linked to RA is located in a gene that codes for an enzyme (called PTPN22) that is known to be involved in controlling the activation of immune cells called T cells. Under normal conditions, the enzyme works as a "negative regulator" --- meaning it inactivates a specific signaling molecule, which in turn interrupts the communication lines and keeps immune cells from becoming overactive. In cases where the SNP is present in one or both copies of an individual's genes for this enzyme, the team found that the negative regulation by this enzyme appears to be inefficient,
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Contact: Christina Verni
cverni@nshs.edu
516-562-1232
North Shore-Long Island Jewish (LIJ) Health System
24-Jun-2004


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