RT Journal Article
SR Electronic
T1 Genetic basis for increased intestinal permeability in families with Crohn’s disease: role of <em>CARD15</em> 3020insC mutation?
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 342
OP 347
DO 10.1136/gut.2005.065557
VO 55
IS 3
A1 Buhner, S
A1 Buning, C
A1 Genschel, J
A1 Kling, K
A1 Herrmann, D
A1 Dignass, A
A1 Kuechler, I
A1 Krueger, S
A1 Schmidt, H H-J
A1 Lochs, H
YR 2006
UL http://gut.bmj.com/content/55/3/342.abstract
AB Background and aim: 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.