A variant in the nuclear dot protein 52kDa gene increases the risk for spontaneous bacterial peritonitis in patients with alcoholic liver cirrhosis

Research output: Contribution to journalArticlepeer-review

Authors

  • Philipp Lutz
  • Benjamin Krämer
  • Dominik J Kaczmarek
  • Marc P Hübner
  • Bettina Langhans
  • And 7 others
  • Beate Appenrodt
  • Frank Lammert
  • Jacob Nattermann
  • Achim Hoerauf
  • Christian P Strassburg
  • Ulrich Spengler
  • Hans Dieter Nischalke

Colleges, School and Institutes

Abstract

BACKGROUND: Spontaneous bacterial peritonitis is frequently a fatal infection in patients with liver cirrhosis. We investigated if nuclear dot protein 52kDa (NDP52), a negative regulator of toll-like receptor (TLR) signalling and autophagy adaptor protein, might be involved.

METHODS: Two cohorts comprising 152 (derivation cohort) and 198 patients (validation cohort) with decompensated liver cirrhosis and 168 healthy controls were genotyped for the rs2303015 polymorphism in the NDP52 gene and prospectively followed-up for spontaneous bacterial peritonitis.

RESULTS: Overall, 57 (38%) patients in the derivation cohort and 77 (39%) in the validation cohort had spontaneous bacterial peritonitis. Cirrhosis was due to alcohol abuse in 57% of the derivation and 66% of the validation cohort. In patients with alcoholic cirrhosis, patients with spontaneous bacterial peritonitis had an increased frequency of the NDP52 rs2303015 minor variant in the derivation (p=0.04) and in the validation cohort (p=0.01). Multivariate analysis confirmed this minor variant (odds ratio 4.7, p=0.002) and the TLR2 -16934 TT variant (odds ratio 2.5, p=0.008) as risk factors for spontaneous bacterial peritonitis. In addition, presence of the NDP52 minor variant affected survival negatively.

CONCLUSION: Presence of the NDP52 rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.

Details

Original languageEnglish
Pages (from-to)62-8
Number of pages7
JournalDigestive and Liver Disease
Volume48
Issue number1
Early online date28 Sep 2015
Publication statusPublished - Jan 2016

Keywords

  • Ascites, Autophagy, NDP52, SBP, rs2303015