{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:00:57Z","timestamp":1761663657962,"version":"3.37.3"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of High Education and Scientific Research of Tunisia"},{"name":"Habib Bourguiba University Hospital of Sfax"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Digest Diseases"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>The common association between <jats:italic>NOD2\/CARD15<\/jats:italic> and <jats:italic>TLR4<\/jats:italic> gene variants with inflammatory bowel disease (IBD) has not been replicated in all studies. We studied the polymorphism of these two genes in Tunisian patients with IBD.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Polymorphisms of <jats:italic>NOD2<\/jats:italic> (R702W, G908R and L1007fs) and <jats:italic>TLR4<\/jats:italic> (Asp299Gly and Thr399Ile) genes were analyzed in 106 patients with IBD (68 with ulcerative colitis [UC], 38 with Crohn's disease [CD]) and 160 healthy controls using polymerase chain reaction\u2010restriction fragment length polymorphism. Genotypes and phenotypes were correlated.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The mutated allele of <jats:italic>TLR4\u2010Thr399Ile<\/jats:italic> was strongly associated with IBD (9.4% in IBD, 7.4% in UC and 13.2% in CD <jats:italic>vs<\/jats:italic> 2.5% in controls; <jats:italic>P<\/jats:italic> = 0.0004, 0.014 and 0.00006, respectively). Heterozygous genotypes were significantly more frequent in patients with IBD (17.0%), UC (14.7%) and CD (21.1%) than in controls (5.0%) (<jats:italic>P<\/jats:italic> = 0.0012, 0.012 and 0.001, respectively). Interestingly, the wild genotype was found to be protective (odds ratio 0.24). The mutated allele of <jats:italic>TLR4\u2010Asp299Gly<\/jats:italic> was more frequent in controls (6.8%) than in patients with IBD (2.9%). A phenotypic correlation of <jats:italic>Asp299Gly\u2010AG<\/jats:italic> genotype with arthritis in UC patients was detected (<jats:italic>P<\/jats:italic> = 0.003). Regarding the <jats:italic>NOD2<\/jats:italic> gene, the common variations studied were not polymorphic and there was no genetic association with IBD.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The <jats:italic>TLR4\u2010Thr399Ile<\/jats:italic> variant was strongly associated with susceptibility to IBD, whereas <jats:italic>TLR4\u2010Asp299Gly<\/jats:italic> seems to play a role in the clinical expression of UC. The rarity and non\u2010association of <jats:italic>NOD2<\/jats:italic> mutations with IBD may reveal a genetic characteristic of the population in our region.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1751-2980.12552","type":"journal-article","created":{"date-parts":[[2017,10,21]],"date-time":"2017-10-21T02:02:47Z","timestamp":1508551367000},"page":"625-633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-5968","authenticated-orcid":false,"given":"Sawsan","family":"Feki","sequence":"first","affiliation":[{"name":"Department of Immunology Habib Bourguiba University Hospital  Sfax 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