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 23 February 2018

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News

Genetic basis for intestinal permeability in IBD families

In healthy first degree relatives of patients with Crohn's disease, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation, reports this month's Gut.

News image

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A genetically impaired intestinal barrier function has long been suspected to be a predisposing factor for Crohn's disease.

Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with Crohn's disease.

Dr Sabine Buehner and colleagues from Germany hypothesized that a CARD15 mutation may be associated with an impaired intestinal barrier.

The researchers studied 128 patients with quiescent Crohn's disease.

The team also assessed 129 first degree relatives, 66 non-related household members, and 96 healthy controls.

The 3 most common CARD15 polymorphisms of R702W, G908R, and 3020insC were analyzed.

The research team determined intestinal permeability by the lactulose/mannitol ratio.

Intestinal permeability was significantly increased in Crohn's disease patients and the relatives compared with household members and controls.

Values above the normal range were seen in 44% of Crohn's disease patients and 26% of relatives.

75% of relatives with 3020insC and R702W mutations had increased intestinal permeability
Gut

However, the team observed above normal range values in only of household members, and in none of the controls.

A household community with Crohn's patients was not associated with increased intestinal permeability in family members.

The team noted that 40% of Crohn's disease first degree relatives carried a CARD15 3020insC mutation.

The researchers also found that 75% of those relatives with combined 3020insC and R702W mutations had increased intestinal permeability.

This was compared with only 15% of wild-types, indicating a genetic influence on barrier function.

The team found that R702W and G908R mutations were not associated with high permeability.

Dr Buehner's team concluded, “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 inflammatory bowel diseases.”

Gut 2006: 55: 342-7
23 February 2006

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