ࡱ> :<;@ bjbjFF 9$,,~~~~~~~2$RL> $*R| ~~~MMM:~~MMM~~MF ^(#Mq0M 9  M~~~~ ~M$"M6JC  HYPERLINK "Javascript:ClickThumbnail(4)"  INCLUDEPICTURE "http://galena/arc%20Logos%20and%20Signatures/_t/arc%20logo_jpg.jpg" \* MERGEFORMATINET  Multiple genes found to play major role in knee osteoarthritis Eight genes have been identified as playing a major part in the development of osteoarthritis of the knee in a study of 1,200 UK patients published in the leading journal Arthritis & Rheumatism today. According to Professor Tim Spector, lead investigator at the Twins Research Unit at St Thomass Hospital in London, it is likely that osteoarthritis of the knee is affected by several genes acting together and many more remain to be uncovered. Professor Spector said: Our findings will help in the development of diagnostic genetic markers to predict the risk of developing knee osteoarthritis or it progressing rapidly. These genes can now also be pursued with confidence to uncover new mechanisms that could lead to new drugs. Osteoarthritis (OA) is the most common cause of musculoskeletal disability related to aging. Arthritis Research Campaign-sponsored twin studies have previously shown osteoarthritis of the knee to be highly heritable, and several genes have been shown over recent years to be associated with risk of this disease in single populations. Unfortunately, many of those genes, when tested in different populations, give inconsistent results. The main objective of the research published this week, also funded by the UK charity, was to identify genetic variants that were consistently associated with clinical knee osteoarthritis by looking at the largest group of subjects studied to date: 600 women and 600 men from Oxford, Nottingham and London, half of whom were healthy and half of whom were diagnosed with osteoarthritis of the knee. Researchers examined 25 genetic variants in twelve different genes. These genes had been previously identified to affect the susceptibility and progression of radiographic osteoarthritis of the knee in a longitudinal study. The genes were originally selected by comparing the gene expression levels between normal and osteoarthritis-affected cartilage tissue. The genes tested were: AACT, ADAM12, BMP2, CD36, CILP, COX2, ESR1, NCOR2, OPG, TNA, TNFAIP6 and VDR. Eight of the genes were found to significantly affect the risk of knee OA in women and five in men. The genes showing the strongest influence on knee OA in women were ADAM12 (a protease enzyme) and ESR1 (an estrogen receptor). The same ADAM12 gene and a variant in the CILP gene (which encodes a cartilage protein) were the strongest associations in men. This study shows that eight genes with a role in cartilage were consistently associated with increased risk of clinical knee OA. It is likely that OA is affected by several genes acting together and many more remain to be uncovered. The work is planned to continue by collecting more subjects and recruiting more adult twins for the genetic studies whether they have arthritis or not. Professor Spector has played a major role in establishing that osteoarthritis has a genetic cause, as well as other factors such as obesity and previous cartilage damage, over the past decade. The Arthritis Research Campaign has funded much of his research. Any twins (identical or non-identical) aged over 16 and would like to join the volunteers on the study can call the Twin Research Unit on 0207 188 5555 or go to  HYPERLINK "http://www.twinsuk.ac.uk" www.twinsuk.ac.uk ENDS Editors Note: For more information please contact Arthritis Research Campaign press officer Jane Tadman on 01246 541107 or 0797 4203828. 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