摘要
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% ofwild-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 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% ofwild-types, indicating a genetic influence on barrier function. RT02W 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.
