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

作者：Juengst Christoph; Stadlbauer Vanessa; Reichert Matthias C; Zimmer Vincent; Weber Susanne N; Ofner Ziegenfuss Lisa; Voigtlaender Torsten; Spindelboeck Walter; Fickert Peter; Kirchner Gabriele I; Lammert Frank; Lankisch Tim O; Krawczyk Marcin

来源：Scientific Reports, 2017, 7(1): 7026.

DOI：10.1038/s41598-017-06268-y

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.

• 出版日期2017-8-1