{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T16:23:27Z","timestamp":1781454207837,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,2,28]],"date-time":"2003-02-28T00:00:00Z","timestamp":1046390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Association of Crohn's and Colitis, UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2003,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Experimental evidence suggests that inappropriate regulation of tumor necrosis factor \u03b1 (TNF\u03b1) may play a role in the pathogenesis of Beh\u00e7et's disease (BD). This is supported by recent reports highlighting the efficacy of anti\u2010TNF\u03b1 agents in the treatment of this disease. The <jats:italic>TNF<\/jats:italic> gene is encoded in the class III region of the HLA complex adjacent to <jats:italic>HLA\u2013B<\/jats:italic>. This genetic proximity to a gene that is already widely implicated in disease susceptibility led us to investigate the association between <jats:italic>TNF<\/jats:italic> promoter polymorphisms and susceptibility to BD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 133 UK white Caucasoid patients with BD and 354 healthy controls. We attempted to dissect the contribution of individual polymorphisms in this gene\u2010dense region by linkage disequilibrium mapping across 6 adjacent genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report a novel association with the <jats:italic>TNF<\/jats:italic> promoter allele <jats:italic>TNF\u20101031C<\/jats:italic>. Subsequent analysis identified 2 extended HLA haplotypes associated with BD. One of them contained the previously recognized susceptibility gene <jats:italic>HLA\u2013B*51<\/jats:italic>, while the other was defined by <jats:italic>HLA\u2013B*5701<\/jats:italic>. Both of these haplotypes contained the <jats:italic>TNF<\/jats:italic> promoter polymorphism \u2212<jats:italic>1031C<\/jats:italic>, an allele that was associated with disease even in individuals who did not carry either <jats:italic>HLA\u2013B*51<\/jats:italic> or <jats:italic>HLA\u2013B*5701<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>TNF\u20101031C<\/jats:italic> allele is independently associated with susceptibility to BD in Caucasoid patients. Further studies will be required to determine the functional effects of this polymorphism, its influence in disease pathogenesis, and its role in other ethnic groups.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10815","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T22:50:19Z","timestamp":1048027819000},"page":"807-813","source":"Crossref","is-referenced-by-count":110,"title":["Mapping the HLA association in Beh\u00e7et's disease: A role for tumor necrosis factor polymorphisms?"],"prefix":"10.1002","volume":"48","author":[{"given":"Tariq","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham 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