{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:56:47Z","timestamp":1791262607613,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T00:00:00Z","timestamp":1112832000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To confirm the association of 2 variants of the Frizzled\u2010related protein gene (<jats:italic>FRZB<\/jats:italic>) with osteoarthritis (OA) of the hip, and to investigate whether these variants also associate with other heritable generalized OA phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An association analysis of 2 variants (R200W and R324G) of <jats:italic>FRZB<\/jats:italic> was performed in a random sample of 1,369 subjects (ages 55\u201370 years) from a population\u2010based cohort (the Rotterdam Study) scored for radiographic characteristics of OA in the hip, hand, spine, and knee and in a patient population of Caucasian probands (ages 40\u201370 years) and their siblings selected for the presence of primary symptomatic OA at multiple sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The allele frequency of the 2 variants was not significantly different between subjects with hip radiographic OA (ROA) and controls. The frequency of the G allele of the R324G variant was significantly increased in subjects with generalized ROA from the Rotterdam Study (0.10) and in subjects from the Genetics, osteoARthritis and Progression study (0.11) compared with that in controls from the Rotterdam Study (0.08). Carriers of this G allele had increased susceptibility for generalized ROA (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 0.9\u20131.9, <jats:italic>P<\/jats:italic> = 0.10) or familial symptomatic OA at multiple sites (OR 1.6, 95% CI 1.1\u20132.3, <jats:italic>P<\/jats:italic> = 0.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results confirm that the R324G variant of the <jats:italic>FRZB<\/jats:italic> gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes. A more extended OA phenotype may indeed be expected from genetic variation in an essential pathway of skeletal development such as Wnt signaling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20993","type":"journal-article","created":{"date-parts":[[2005,4,7]],"date-time":"2005-04-07T15:23:19Z","timestamp":1112887399000},"page":"1077-1080","source":"Crossref","is-referenced-by-count":108,"title":["Association of the frizzled\u2010related protein gene with symptomatic osteoarthritis at multiple sites"],"prefix":"10.1002","volume":"52","author":[{"given":"J. L.","family":"Min","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Meulenbelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Riyazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kloppenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Houwing\u2010Duistermaat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. B.","family":"Seymour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. A.","family":"Pols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"van Duijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. E.","family":"Slagboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,4,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200309000-00019"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200103000-00004"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199908)42:8<1729::AID-ANR23>3.0.CO;2-H"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/41.8.955"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.42.26131"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0802"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10136"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403456101"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00145007"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020006909285"},{"key":"e_1_2_5_12_2","series-title":"The epidemiology of chronic rheumatism","volume-title":"Atlas of standard radiographs of arthritis","author":"Kellgren JH","year":"1963"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.024661"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1529-8817.2003.00085.x"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.20993","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.20993","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:40:45Z","timestamp":1697056845000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.20993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4]]},"references-count":13,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,4]]}},"alternative-id":["10.1002\/art.20993"],"URL":"https:\/\/doi.org\/10.1002\/art.20993","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4]]}}}