{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:18:08Z","timestamp":1791177488713,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,8,5]],"date-time":"2004-08-05T00:00:00Z","timestamp":1091664000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Osteoarthritis (OA), characterized by late\u2010onset degeneration of articular cartilage, is recognized to have a genetic component. We examined the role of 26 single\u2010nucleotide polymorphisms (SNPs) from 24 candidate genes in OA susceptibility and progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared human complementary DNA libraries from OA\u2010affected and normal cartilage and synovium and selected 22 genes in addition to the estrogen receptor \u03b1 and vitamin D receptor genes. Based on the availability of polymorphisms, we proceeded to test whether genetic variation at those genes affected susceptibility to or progression of radiographic knee OA over a 10\u2010year period in 749 women (mean age 64 years) from the longitudinal Chingford Study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After adjusting for age and body mass index, we observed significant associations at <jats:italic>ADAM12<\/jats:italic>, <jats:italic>BMP2<\/jats:italic>, <jats:italic>CD36<\/jats:italic>, <jats:italic>COX2<\/jats:italic>, and <jats:italic>NCOR2<\/jats:italic> with 3 OA susceptibility traits (presence\/absence of joint space narrowing [JSN], presence\/absence of osteophytes, and Kellgren\/Lawrence [K\/L] score). For the OA progression traits (change over 10 years in the K\/L score, osteophyte grade, and JSN grade), we found significant associations with <jats:italic>ADAM12<\/jats:italic>, <jats:italic>CILP<\/jats:italic>, <jats:italic>OPG<\/jats:italic>, and <jats:italic>TNA<\/jats:italic>. Overall, we observed 15 associations with nominal significance (<jats:italic>P<\/jats:italic> &lt; 0.05) and, by permutation analysis, found that such a number would be observed by chance only 3.8% of the time. Although these tests require replication, the stronger genetic associations observed are unlikely to be attributable simply to multiple comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that OA severity and progression have a multigenic and feature\u2010specific nature. These findings should encourage the development of genetic diagnostics for OA progression based on multiple SNPs and help unravel some of the complex disease mechanisms in OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20443","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T20:02:14Z","timestamp":1092081734000},"page":"2497-2507","source":"Crossref","is-referenced-by-count":145,"title":["Association study of candidate genes for the prevalence and progression of knee osteoarthritis"],"prefix":"10.1002","volume":"50","author":[{"given":"Ana M.","family":"Valdes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen 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