Inflammatory bowel disease: crossroads of microbes, by Jamie Goode

By Jamie Goode

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The variant alleles do not appear to determine the severity of ileal or ¢brostenosing disease, as judged by the time to ¢rst surgery (Brant et al 2003) or surgical recurrence (Ahmad et al 2002a). It is not yet clear how NOD2/CARD15 variants cause ileal or ¢brostenosing disease but the recent demonstration of NOD2/CARD15 expression by Paneth cells, which are located predominately in the terminal ileum provides a tantalizing clue. Association with familial disease? Several epidemiological studies have reported a higher incidence of ileal or ileocolonic disease in familial cases of CD (Colombel et al 1996, Cottone et al 1997, Halme et al 2002).

Nat Genet 29:223^228 Roussomoustakaki M, Satsangi J, Welsh K et al 1997 Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology 112:1845^1853 Sachar DB, Andrews HA, Farmer RG et al 1992 Proposed classi¢cation of patient subgroups in Crohn’s disease. Gastroenterol Int 5:141^154 Satsangi J, Grootscholten C, Holt H, Jewell DP 1996a Clinical patterns of familial in£ammatory bowel disease. Gut 38:738^741 Satsangi J, Welsh KI, Bunce M et al 1996b Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in in£ammatory bowel disease.

Clin Exp Immunol 115:294^300 Brant SR, Picco MF, Achkar JP et al 2003 De¢ning complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn’s disease phenotypes. In£amm Bowel Dis 9:281^289 Carter MJ, di Giovine FS, Jones S et al 2001a Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians. Gut 48:461^467 PHENOTYPE-DETERMINING GENES 27 Carter MJ, Di Giovine FS, Cox A et al 2001b The interleukin 1 receptor antagonist gene allele 2 as a predictor of pouchitis following colectomy and IPAA in ulcerative colitis.

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