New study finds genetic causes of osteoarthritis Scientists at 缅北禁地 have discovered more genetic regions associated with the cause of osteoarthritis. Researchers have described the findings as a significant breakthrough in understanding the genetic risk factors that cause the disease. Publishing their findings in The Lancet today the Arthritis Research UK-funded arcOGEN consortium of nine institutions across the UK has highlighted eight genetic regions linked to the development of osteoarthritis. Previously only three osteoarthritis genetic regions had been identified. Several of the genetic regions encompass genes that are known to regulate how joints are made and then maintained, making them excellent osteoarthritis candidate gene. Another genetic region contains a gene involved in the regulation of body weight, which is a strong risk factor for osteoarthritis.Principal investigator of arcOGEN , professor of musculoskeletal research at 缅北禁地, said: 鈥淲e know that osteoarthritis runs in families and that this is due to the genes that people pass on, rather than their shared environment. In this study we were able to say with a high degree of confidence which genetic regions are the major risk factors for developing osteoarthritis: the first time that this has been possible for this common yet complex disease. It鈥檚 an important first step.鈥�The £2.2million project is the world鈥檚 biggest ever-genome wide study into osteoarthritis, comparing the genetic differences of 7,400 patients with severe osteoarthritis with 11,000 healthy volunteers. The results were then replicated in over 7,000 OA individuals and 43,000 control individuals, from four European collaborating partners.Osteoarthritis affects around 40 per cent of people over the age of 70, a total of 8 million people in the UK, causing pain and disability. There is currently no cure for the condition. Treatments for early osteoarthritis are limited to non-surgical options such as pain killers and physiotherapy until joint replacement becomes a viable option. Osteoarthritis is a complex disorder with both environmental and genetic causes. It is estimated that about 50 per cent of an individual鈥檚 risk of developing osteoarthritis is due to inherited genetic factors.Jacqueline Macmillan, 54, from Beadnall, Northumberland suffers from hip osteoarthritis. The condition came on very suddenly at the age of 50, and her hip literally disintegrated within weeks. She had her first hip replacement within three months of being diagnosed when she was 50, and her second at the age of 53. Both operations have been very successful.She was involved in arcOGEN and gave blood samples to researchers in 缅北禁地 running the project.She says: 鈥淭he pain I went through in this short period of time I would not wish on my worst enemy. You can鈥檛 do anything to get rid of it, and it affects everything you try to do. Some days I felt that I couldn鈥檛 even get out of bed. As soon as I put my foot on the floor I鈥檇 get this, awful grating pain.鈥淚 was lucky as I was able to have surgery quickly, but I can鈥檛 imagine having to put up with that sort of pain for years.鈥淚f it were possible to be able to predict who gets arthritis, it would mean they could change their lifestyle 鈥� lose weight, become more active, and so on. It wouldn鈥檛 have helped me as my OA came on so quickly, but at least it wouldn鈥檛 have been such a shock.鈥�Two of the novel regions are close to genes that immediately suggest clinical implications for osteoarthritis. One, CHST11, affects cartilage proteoglycan (proteins in the cartilage modified with sugar chemicals) and changes in proteoglycan are an active area of development of new treatments for osteoarthritis. A second gene, PTHLH, is the basis for recently developed parathyroid hormone-based treatments for osteoporosis. The research team suggest a next step would be to explore whether these compounds may also be effective in osteoarthritis.Dr Ele Zeggini, first and senior co-author on the research from the Wellcome Trust Sanger Institute, said: 鈥淲e discovered eight new regions that might contribute to osteoarthritis, several of which might be involved in the development, production or maintenance of healthy cartilage. They provide a fascinating insight into the processes that could contribute to this disease and 鈥� importantly 鈥� our list of genetic culprits also helps us to begin to pick apart this challenging disease, opening a door which could lead to treatments targeted to specific types of osteoarthritis.鈥�Medical director of Professor Alan Silman said: 鈥淭here is no cure for osteoarthritis yet it affects millions of people around the world. For 60 years we have known that you are twice as likely to have osteoarthritis if your parents have the disease, yet we haven鈥檛 known why. 鈥淯ntil we understand the cause of this complex disease, we cannot hope to find a cure. This is a major breakthrough in our understanding of osteoarthritis which we hope will help us to unlock the genetic basis of the disease.鈥�Further work is now needed to pinpoint the actual DNA changes within the genetic regions to establish exactly how these changes lead to osteoarthritis.Professor Loughlin said that they were not yet able to use their discoveries as a tool to predict who was more or less likely to develop the disease, or to predict the degree of osteoarthritis severity, based on the genes they have inherited. Far more genes are involved in causing disease susceptibility than was previously thought, and there are still many left to find.Professor Loughlin added: 鈥淗owever, what we are able to do is to use our genetic discoveries to identify key biological pathways that can now be exploited to develop new treatments.鈥�More information can be found here about the on the webpages. published on: 3 July 2012
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