Z Gastroenterol 2017; 55(08): e57-e299
DOI: 10.1055/s-0037-1604988
Kurzvorträge
Leber und Galle
Genetische Suszeptibilitätsfaktoren von Lebererkrankungen: Donnerstag, 14 September 2017, 08:00 – 09:20, St. Petersburg/Forschungsforum 1
Georg Thieme Verlag KG Stuttgart · New York

NOD2 gene variants as novel risk factors for secondary sclerosing cholangitis in critically ill patients

C Jüngst
1   Department of Medicine II, Saarland University, Saarland University Medical Center, Homburg, Deutschland
,
V Stadlbauer
2   Division of Gastroenterology und Hepatology, Medical University of Graz, Graz, Österreich
,
M Reichert
1   Department of Medicine II, Saarland University, Saarland University Medical Center, Homburg, Deutschland
,
V Zimmer
1   Department of Medicine II, Saarland University, Saarland University Medical Center, Homburg, Deutschland
,
S Weber
1   Department of Medicine II, Saarland University, Saarland University Medical Center, Homburg, Deutschland
,
L Ofner-Ziegenfuß
3   Institute of Human Genetics, Medical University of Graz, Graz, Deutschland
,
T Voigtländer
4   Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Deutschland
,
W Spindelböck
2   Division of Gastroenterology und Hepatology, Medical University of Graz, Graz, Österreich
,
P Fickert
2   Division of Gastroenterology und Hepatology, Medical University of Graz, Graz, Österreich
,
G Kirchner
5   Department of Internal Medicine I, University of Regensburg, Regensburg, Deutschland
,
F Lammert
1   Department of Medicine II, Saarland University, Saarland University Medical Center, Homburg, Deutschland
,
T Lankisch
4   Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Deutschland
,
M Krawczyk
1   Department of Medicine II, Saarland University, Saarland University Medical Center, Homburg, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2017 (online)

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Background:

Sclerosing cholangitis in critically ill patients (SC-CIP) is a chronic cholestatic disease often progressing to liver cirrhosis. Biliary tract infections and bile acid toxicity might be involved in the pathogenesis. We hypothesized that genetic risk factors increase the odds of developing SC-CIP. Therefore it was our aim to investigate common NOD2 (nucleotide-binding oligomerisation domain containing 2) gene variants, known risk factors for Crohn's disease and bacterial intestinal translocation, variants of hepatobiliary transporter genes and the common PNPLA3 risk variant, which have been associated with chronic liver diseases.

Patients and methods:

By screening of 4,641 endoscopic retrograde cholangiography procedures we identified 17 patients (14 men, median age 63 years) with SC-CIP (Cohort 1, discovery cohort). In these patients we analyzed the three common NOD2 risk variants and subsequently validated the data by testing the NOD2 variants in 29 patients from three other German and Austrian academic centers (Cohort 2, replication cohort). In addition, common procholestatic polymorphisms in hepatocanalicular transporter genes and the PNPLA3 p.I148 M variant were investigated in both cohorts.

Results:

The NOD2 variants were present in 5 of the 17 SC-CIP patients (29.4%) in Cohort 1, which is twice as high as in the general population. Four patients were carriers of the p.R702W variant and the c.3020insC variant was present in one patient. The genetic association was replicated in Cohort 2 with 8 patients (27.6%) harboring NOD2 variants. In contrast, neither ATP8B1, ABCB4 or ABCB11 polymorphisms nor the PNPLA3 p.I148 M variant did show consistent associations with SC-CIP development.

Conclusions:

This first report on genetic risk factors in SC-CIP patients shows an extraordinary high frequency of NOD2 variation. These results suggest a critical role of impaired intestinal anti-bacterial defense for the development of SC-CIP.