BACKGROUND AND AIMS: A genetically impaired intestinal barrier function has long been suspected to be a predisposing factor for Crohn's disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. METHODS: We studied 128 patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related household members (CD-NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC) were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. RESULTS: Intestinal permeability was significantly increased in CD and CD-R groups compared with CD-NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD-R but only in 6% of CD-NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD-R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% of wild-types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. CONCLUSIONS: In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD.
BACKGROUND AND AIMS: A genetically impaired intestinal barrier function has long been suspected to be a predisposing factor for Crohn's disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. METHODS: We studied 128 patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related household members (CD-NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC) were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. RESULTS: Intestinal permeability was significantly increased in CD and CD-R groups compared with CD-NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD-R but only in 6% of CD-NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD153020insC mutation and 75% (3/4) of those CD-R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% of wild-types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. CONCLUSIONS: In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD153020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD.
Authors: M Peeters; B Geypens; D Claus; H Nevens; Y Ghoos; G Verbeke; F Baert; S Vermeire; R Vlietinck; P Rutgeerts Journal: Gastroenterology Date: 1997-09 Impact factor: 22.682
Authors: K D Katz; D Hollander; C M Vadheim; C McElree; T Delahunty; V D Dadufalza; P Krugliak; J I Rotter Journal: Gastroenterology Date: 1989-10 Impact factor: 22.682
Authors: C Büning; J Genschel; S Bühner; S Krüger; K Kling; A Dignass; P Baier; B Bochow; J Ockenga; H H-J Schmidt; H Lochs Journal: Aliment Pharmacol Ther Date: 2004-05-15 Impact factor: 8.171
Authors: Matthias Jürgens; Stephan Brand; Rüdiger P Laubender; Julia Seiderer; Jürgen Glas; Martin Wetzke; Johanna Wagner; Simone Pfennig; Cornelia Tillack; Florian Beigel; Maria Weidinger; Fabian Schnitzler; Martin E Kreis; Burkhard Göke; Peter Lohse; Karin Herrmann; Thomas Ochsenkühn Journal: J Gastroenterol Date: 2010-04-29 Impact factor: 7.527