4.5 Article

The JAK2 variant rs10758669 in Crohn's disease: altering the intestinal barrier as one mechanism of action

Journal

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
Volume 27, Issue 5, Pages 565-573

Publisher

SPRINGER
DOI: 10.1007/s00384-011-1345-y

Keywords

Crohn's disease; Ulcerative colitis; Inflammatory bowel disease; JAK2; STAT3; IRGM; Intestinal permeability

Funding

  1. Eli and Edythe Broad Foundation [IBD-0164R]
  2. German Ministry for Education and Research (BMBF)-Competence Network Inflammatory Bowel Disease [01GI0284 TP 1.17]
  3. Forschungsforderung of the Charite, Universitatsmedizin Berlin

Ask authors/readers for more resources

The aetiology of intestinal barrier dysfunction in Crohn's disease (CD) is poorly understood. Associations in relatives of CD families suggest a genetic basis, but the relevant variants are still unknown. We hypothesized that variants in genes occurring in pathways such as autophagy and IL23 signalling might contribute to CD by altering intestinal permeability. We analysed five variants (rs10758669 within JAK2, rs744166 within STAT3, rs4958847, rs11747270 and rs13361189 within IRGM) in adult German inflammatory bowel disease patients (CD, n = 464; ulcerative colitis (UC), n = 292) and matched healthy controls (n = 508). These data were correlated with gastrointestinal permeability as assessed by lactulose/mannitol ratio in CD patients (n = 141) in remission. Our data confirm the association between JAK2 rs10758669 (p = 0.026, OR = 1.25, 95% CI = 1.04-1.50) and STAT3 rs744166 (p = 0.04, OR = 0.83, 95% CI = 0.688-0.998) with CD, but not UC. With respect to all the analysed IRGM variants, no association was found to either CD or UC. Among CD patients, an increased intestinal permeability was detected in 65 out of 141 patients (46.1%). Most importantly, patients carrying the C risk allele within JAK2 rs10758669 displayed an increased permeability more often compared with patients without the C allele (p = 0.004). No association with intestinal permeability was found for STAT3 rs744166 and all IRGM variants. JAK2 rs10758669 and STAT3 rs744166 increase susceptibility for CD. We show that the A > C substitution in rs10758669 of the JAK2 gene is associated with increased intestinal permeability. Altering intestinal barrier function might thus be one mechanism how JAK2 contributes to CD pathogenesis.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available