{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:51:31Z","timestamp":1791103891799,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2002,6,6]],"date-time":"2002-06-06T00:00:00Z","timestamp":1023321600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the role of the gene <jats:italic>NOD2<\/jats:italic> in susceptibility to, and clinical manifestations of, ankylosing spondylitis (AS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A case\u2013control study of <jats:italic>NOD2<\/jats:italic> polymorphisms known to be associated with Crohn's disease (CD) (Pro<jats:sup>268<\/jats:sup>Ser, Arg<jats:sup>702<\/jats:sup>Trp, Gly<jats:sup>908<\/jats:sup>Arg, and Leu<jats:sup>1007<\/jats:sup>fsinsC) was performed in 229 cases of primary AS with no diagnosed inflammatory bowel disease (IBD), 197 cases of AS associated with IBD (referred to as colitic spondylarthritis; comprising 78 with CD and 119 with ulcerative colitis [UC]), and 229 ethnically matched, healthy controls. Associations between <jats:italic>NOD2<\/jats:italic> polymorphisms and several clinical features of AS, including disease severity assessed by questionnaire and age at spondylarthritis onset, were also investigated. Exclusion linkage mapping of chromosome 16 was performed in a separate group of 185 multicase families with AS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An association was identified between Gly<jats:sup>908<\/jats:sup>Arg and UC spondylarthritis (<jats:italic>P<\/jats:italic> = 0.016, odds ratio [OR] 4.6, 95% confidence interval [95% CI] 1.3\u201316), and a nonsignificant trend with a similar magnitude was observed in association with CD spondylarthritis (<jats:italic>P<\/jats:italic> = 0.08, OR 3.9, 95% CI 0.8\u201318). The Pro<jats:sup>268<\/jats:sup>Ser variant was inversely associated with UC spondylarthritis (<jats:italic>P<\/jats:italic> = 0.003, OR 0.55, 95% CI 0.37\u20130.82), but not with CD spondylarthritis. No association was demonstrated between <jats:italic>NOD2<\/jats:italic> variants and primary AS, or between other variants of <jats:italic>NOD2<\/jats:italic> and either UC or CD spondylarthritis. Carriage of the Pro<jats:sup>268<\/jats:sup>Ser polymorphism was associated with greater disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (<jats:italic>P<\/jats:italic> = 0.002). Although patients with CD had a younger age at spondylarthritis onset than did those with UC (22.4 years versus 26.4 years; <jats:italic>P<\/jats:italic> = 0.01), no association was noted between the <jats:italic>NOD2<\/jats:italic> variants linked with CD and age at spondylarthritis onset. In primary AS, the presence of a gene with a magnitude of association &gt;2.0 was excluded (exclusion logarithm of odds score less than \u22122.0), and no association was observed with the microsatellite D16S3136.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>NOD2<\/jats:italic> variants do not significantly affect the risk of developing primary AS, but may influence susceptibility to, and clinical manifestations of, colitic spondylarthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10329","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T12:29:56Z","timestamp":1033907396000},"page":"1629-1633","source":"Crossref","is-referenced-by-count":70,"title":["Role of <i>NOD2<\/i> variants in spondylarthritis"],"prefix":"10.1002","volume":"46","author":[{"given":"Alison M.","family":"Crane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Bradbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"van Heel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dermot P. B.","family":"McGovern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinead","family":"Brophy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Siminovitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Paul","family":"Wordsworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Calin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,6,6]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"2860","article-title":"Spondyloarthropathy is underestimated in inflammatory bowel disease: prevalence and HLA association","volume":"27","author":"De Vlam K","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_6_3_2","first-page":"330","article-title":"Enteropathic spondylarthritis in chronic inflammatory bowel diseases: prevalence, manifestation pattern and HLA association","volume":"91","author":"Protzer U","year":"1996","journal-title":"Med Klin"},{"key":"e_1_2_6_4_2","first-page":"2279","article-title":"The evolution of spondyloarthropathies in relation to gut histology. 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