Manchester finds gene associated with RA

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MANCHESTER, U.K.—In early November, University of Manchester researchers announced they had identified a genetic variant in a region on chromosome 6 that is associated with rheumatoid arthritis (RA), the most common inflammatory arthritis, affecting 387,000 people in the United Kingdom alone.
Prof. Jane Worthington's team at the Arthritis Research Campaign Epidemiology Unit at the university investigated nine genetic regions identified earlier this year as potentially harboring DNA variants determining susceptibility to RA. Association to one of the variants on chromosome 6 was unequivocally confirmed, reported Nature Genetics in its Nov. 4 issue. Although this variant is not located in a gene, Worthington suggests that it may influence the behavior of a nearby gene—tumor necrosis factor associated protein (TNFAIP3)—as this is a gene known to be involved in inflammatory processes.
Worthington and her team made their findings as part of the largest-ever study of the genetics behind common diseases, the £9 million Wellcome Trust Case Control Consortium (WTCCC). The WTCCC study has given a major boost to the understanding of the genetics of seven common diseases, including RA. As well as providing insights into what leads some people to develop the diseases and offering new avenues for treatments, the success of the approach heralds exciting advances in the study of the genetics of disease.
The Manchester team is currently investigating several genomic regions which may be important in the development of RA but the locus near TNFAIP3 is the first to be fully validated. Until recently, only two other genes were known to explain 50 percent of genetically determined susceptibility. Now, the Manchester researchers are working to understand how the variation within the chromosome 6q region influences the development of RA, the course of the disease and the response to treatment.
"This is a very exciting result; the validation of this association takes us one step closer to understanding the genetic risk factors behind what is a debilitating disease for sufferers and an expensive disease for the NHS," says Worthington. "We are indebted to the Arthritis Research Campaign for their longstanding support of this research and for recognizing the importance of establishing large, well-characterized cohorts of RA patients. This study was made possible by the fantastic collaboration of scientists from five other groups around the U.K. who helped us to assemble an impressive cohort of over 5,000 samples from RA patients for this experiment. Their continued collaboration will be significant in ensuring the continued progress of this research."
RA, which affects up to 1 percent of the adult population, is a chronic inflammatory disease that can affect nearly all joints in the body. Complications such as lung disease can occur. In addition, patients with RA are more likely to die from cardiovascular disease and some cancers.

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