NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients

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...

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Autores principales:	Christoph Jüngst, Vanessa Stadlbauer, Matthias C. Reichert, Vincent Zimmer, Susanne N. Weber, Lisa Ofner-Ziegenfuß, Torsten Voigtländer, Walter Spindelböck, Peter Fickert, Gabriele I. Kirchner, Frank Lammert, Tim O. Lankisch, Marcin Krawczyk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a695bed299964c64a45f7272a191bee3
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spelling	oai:doaj.org-article:a695bed299964c64a45f7272a191bee32021-12-02T11:40:32ZNOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients10.1038/s41598-017-06268-y2045-2322https://doaj.org/article/a695bed299964c64a45f7272a191bee32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06268-yhttps://doaj.org/toc/2045-2322Abstract 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.Christoph JüngstVanessa StadlbauerMatthias C. ReichertVincent ZimmerSusanne N. WeberLisa Ofner-ZiegenfußTorsten VoigtländerWalter SpindelböckPeter FickertGabriele I. KirchnerFrank LammertTim O. LankischMarcin KrawczykNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christoph Jüngst Vanessa Stadlbauer Matthias C. Reichert Vincent Zimmer Susanne N. Weber Lisa Ofner-Ziegenfuß Torsten Voigtländer Walter Spindelböck Peter Fickert Gabriele I. Kirchner Frank Lammert Tim O. Lankisch Marcin Krawczyk NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
description	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.
format	article
author	Christoph Jüngst Vanessa Stadlbauer Matthias C. Reichert Vincent Zimmer Susanne N. Weber Lisa Ofner-Ziegenfuß Torsten Voigtländer Walter Spindelböck Peter Fickert Gabriele I. Kirchner Frank Lammert Tim O. Lankisch Marcin Krawczyk
author_facet	Christoph Jüngst Vanessa Stadlbauer Matthias C. Reichert Vincent Zimmer Susanne N. Weber Lisa Ofner-Ziegenfuß Torsten Voigtländer Walter Spindelböck Peter Fickert Gabriele I. Kirchner Frank Lammert Tim O. Lankisch Marcin Krawczyk
author_sort	Christoph Jüngst
title	NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
title_short	NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
title_full	NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
title_fullStr	NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
title_full_unstemmed	NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
title_sort	nod2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a695bed299964c64a45f7272a191bee3
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NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients

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