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International Journal of Colorectal Disease

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01-05-2012 | Original Article

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

Authors: Matthias Prager, Janine Büttner, Verena Haas, Daniel C. Baumgart, Andreas Sturm, Martin Zeitz, Carsten Büning

Published in: International Journal of Colorectal Disease | Issue 5/2012

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Title: The JAK2 variant rs10758669 in Crohn’s disease: altering the intestinal barrier as one mechanism of action
Authors: Matthias Prager
Janine Büttner
Verena Haas
Daniel C. Baumgart
Andreas Sturm
Martin Zeitz
Carsten Büning
Publication date: 01-05-2012
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 5/2012
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-011-1345-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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