Polymorphsims in the farnesoid X receptor modify the risk for spontaneous bacterial peritonitis in cirrhotic patients

HD Nischalke; P Lutz; C Berger; B Langhans; A Hoerauf; F Grünhage; B Appenrodt; F Lammert; J Nattermann; T Sauerbruch; CP Strassburg; U Spengler

doi:10.1055/s-0033-1361043

Zeitschrift für Gastroenterologie, Table of Contents

Polymorphsims in the farnesoid X receptor modify the risk for spontaneous bacterial peritonitis in cirrhotic patients

HD Nischalke ¹, P Lutz ¹, C Berger ¹, B Langhans ¹, A Hoerauf ², F Grünhage ³, B Appenrodt ³, F Lammert ³, J Nattermann ¹, T Sauerbruch ¹, CP Strassburg ¹, U Spengler ¹

¹University of Bonn, Department of Internal Medicine I, Bonn, Germany
²University of Bonn, Institute for Medical Microbiology, Bonn, Germany
³Saarland University, Department of Medicine II, Homburg, Germany

Abstract

Background and Aims:

The farnesoid X receptor (FXR) is involved in bacterial translocation in mice. In humans with liver cirrhosis, bacterial translocation can result in spontaneous bacterial peritonitis (SBP). We hypothesized that polymorphisms in the FXR gene (NR1H4) might influence the risk for SBP.

Methods:

We collected blood for genotyping, clinical and laboratory data of 293 cirrhotic patients with ascites and 226 healthy controls. The NR1H4 rs56163822, rs11110390 and rs12313471 polymorphisms were determined on the LightCycler system.

Results:

In our cohort 115 (39%) patients with liver cirrhosis and ascites had SBP. Distribution of all NR1H4 genotypes matched the Hardy-Weinberg equilibrium. Patients with SBP had a significantly higher frequency of the heterozygous NR1H4 rs56163822 (GT) genotype (7.0%) than patients without SBP (1.7%, OR = 4.4, p = 0.02). Furthermore, the frequency of the NR1H4 rs11110390 C allele was increased in male patients with SBP (75.3% versus 65.6%, OR = 1.60, p = 0.036). Finally, a multivariate Cox-regression analysis confirmed the NR1H4 rs56163822 GT genotype as an independent predictor of SBP (OR = 6.8, p = 0.018).

Conclusion:

The rs56163822 G-1T polymorphism in the FXR gene is a new independent risk factor for SBP in cirrhotic patients. FXR modulators may become a target for prophylaxis of SBP.