Brief Reports
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2005; 11(38): 6031-6037
Published online Oct 14, 2005. doi: 10.3748/wjg.v11.i38.6031
Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection
C Meiler, M Mühlbauer, M Johann, A Hartmann, B Schnabl, N Wodarz, G Schmitz, J Schölmerich, C Hellerbrand
C Meiler, B Schnabl, J Schölmerich, C Hellerbrand, M Mülbauer, Department of Internal Medicine I, University of Regensburg, Regensburg 93042, Germany
M Johann, N Wodarz, Department of Psychiatry, University of Regensburg, Regensburg 93042, Germany
A Hartmann, Department of Pathology, University of Regensburg, Regensburg 93042, Germany
G Schmitz, Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg 93042, Germany
Author contributions: All authors contributed equally to the work.
Supported by grants from the Else Kroner Fresenius-Stiftung to Hellerbrand C and the Deutsche Forschungsgemeinschaft (Schn 620/3-1) to Schnabl B
Correspondence to: C Hellerbrand, MD, Department of Internal Medicine I, University of Regensburg, Regensburg D-93042, Germany. claus.hellerbrand@klinik.uni-regensburg.de
Telephone: +49-941-944-7155 Fax: +49-941-944-7154
Received: March 10, 2004
Revised: April 6, 2005
Accepted: April 9, 2005
Published online: October 14, 2005
Abstract

AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection.

METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls. Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined.

RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading.

CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.

Keywords: CD14 gene, Alcoholic liver disease, Chronic hepatitis C infection