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Researchers identify new risk factor gene for rheumatoid arthritis

Scientists at The Feinstein Institute for Medical Research and a team of collaborators from across the country have identified a new risk factor gene for rheumatoid arthritis. The paper will be published in Nature Genetics and the finding brings light to the nature of the disease. The gene, dubbed REL, is a member of the NF-B family, important transcription factors that have many roles in the body. The NF-B family seems to have a big hand in regulating the body's immune response as well.

"The NF-is a key switching point for many cellular activities," said Peter K. Gregersen, MD, head of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute and lead author of the study. Dr. Gregersen is part of a nationwide consortium of investigators seeking to identify risk genes for rheumatoid arthritis (RA). The hope is to figure out the genetic triggers and identify treatments that block this autoimmune process. In theory, such advances can point the way to understanding other autoimmune disorders. About one percent of the population will develop rheumatoid arthritis, which can be crippling.

REL is a key regulator of CD40, which works through the NF-pathway.

"This paper represents the latest in a series of important publications chronicling an exceptionally productive collaboration between extramural and intramural scientists through the North American Rheumatoid Arthritis Consortium," said Daniel Kastner, MD, PhD, clinical director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. "In describing yet another gene in the CD40 signaling pathway that is involved in rheumatoid arthritis susceptibility, this paper reinforces the possibility of targeting this pathway in selected patients with this debilitating illness."

The consortium has helped identify many genes involved in rheumatoid arthritis but this genetic finding is significant because of its key role in immune system regulation. It did not reveal itself in previous genetic studies because the sample size was just not large enough. In previous studies, genetic samples from about 2,000 patients were used to identify markers associated with risk for RA. In the latest study, the scientists analyzed samples from 4,000 RA patients and controls.

According to Dr. Gregersen, this particular genetic variant is rather common, found in about a third of people in North America. That means that it must confer an important survival advantage. That said, scientists need to figure out its role in increasing the risk for RA. Next on the research agenda is to see if they can measure how the gene is regulated under specific conditions that set the stage for RA. "There are a huge number of unknowns," said Dr. Gregersen. "These findings are clear this pathway is involved but there is a lot of work to be done."

Genetic differences between individuals help scientists understand many diseases. But this is just the beginning, added Dr. Gregersen. Today, most markers that are used to identify genes represent variants that occur in more than five percent of the population. The next wave in genetic screening will have to include the variants that occur in less than one percent of the population.


Contact: Jamie Talan
North Shore-Long Island Jewish (LIJ) Health System

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