The JAK2 variant rs10758669 in Crohn’s disease: altering the intestinal barrier as one mechanism of action
| Autor: | Carsten Büning, Martin Zeitz, Matthias Prager, Daniel C. Baumgart, Verena Haas, Andreas Sturm, Janine Büttner |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male STAT3 Transcription Factor Genotyping Techniques Nod2 Signaling Adaptor Protein Disease Inflammatory bowel disease Permeability Crohn Disease GTP-Binding Proteins Interleukin 23 medicine Humans Genetic Predisposition to Disease Intestinal Mucosa Crohn's disease Intestinal permeability business.industry Autophagy Gastroenterology Janus Kinase 2 medicine.disease Ulcerative colitis Intestinal Absorption Immunology IRGM Colitis Ulcerative Female business Signal Transduction |
| Zdroj: | International Journal of Colorectal Disease. 27:565-573 |
| ISSN: | 1432-1262 0179-1958 |
| DOI: | 10.1007/s00384-011-1345-y |
| Popis: | 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 AC 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. |
| Databáze: | OpenAIRE |
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