Juengst, Christoph and Stadlbauer, Vanessa and Reichert, Matthias C. and Zimmer, Vincent and Weber, Susanne N. and Ofner-Ziegenfuss, Lisa and Voigtlaender, Torsten and Spindelboeck, Walter and Fickert, Peter and Kirchner, Gabriele I. and Lammert, Frank and Lankisch, Tim O. and Krawczyk, Marcin (2017) NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients. SCIENTIFIC REPORTS, 7: 7026. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
Sclerosing cholangitis in critically ill patients (SC-CIP) is a progressive cholestatic disease of unknown aetiology characterized by chronic biliary infections. Hence we hypothesized that common NOD2 (nucleotide-binding oligomerisation domain containing 2) gene variants, known risk factors for Crohn's disease and bacterial translocation in liver cirrhosis, increase the odds of developing SC-CIP. Screening of 4,641 endoscopic retrograde cholangiography procedures identified 17 patients with SC-CIP, who were then genotyped for the three common NOD2 mutations (Cohort 1, discovery cohort). To validate the association, we subsequently tested these NOD2 variants in 29 patients from SC-CIP cohorts of three additional medical centers (Cohort 2, replication cohort). In Cohort 1, the NOD2 variants were present in 5 of 17 SC-CIP patients (29.4%), which is twice the frequency of the general population. These results were replicated in Cohort 2 with 8 patients (27.6%) showing NOD2 mutations. In contrast, polymorphisms of hepatocanalicular transporter genes did not have major impact on SC-CIP risk. This first study on genetic susceptibility in SC-CIP patients shows an extraordinary high frequency of NOD2 variation, pointing to a critical role of inherited impaired anti-bacterial defense in the development of this devastating biliary disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; LIVER-DISEASE; ASSOCIATION; CIRRHOSIS; BILE; MUTATIONS; SEPSIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 25 Feb 2019 14:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1449 |
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