Z Gastroenterol 2007; 45 - A1_13
DOI: 10.1055/s-2007-967767

Association of a common SNP in the complement factor 5 gene with severity of alcoholic liver cirrhosis

F Grünhage 1, S Hillebrandt 1, F Stickel 2, HE Wasmuth 3, T Sauerbruch 1, F Lammert 4
  • 1Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn, Bonn
  • 2Institute of Clinical Pharmacology, University of Berne, Berne, Switzerland
  • 3Department of Internal Medicine III, RWTH Aachen, Aachen
  • 4Medizinische Klinik und Poliklinik I, Universität Bonn, Bonn

Introduction

Progression of liver fibrosis to cirrhosis in alcoholic liver disease is determined by alcohol consumption, gender and genetic factors yet to be defined. We recently identified an association of two haplotype-tagging (ht) SNPs in the complement factor 5 (C5) gene with severity of liver fibrosis in hepatitis C patients and serum C5 levels. Activation of the complement system and induction of pro-inflammatory mechanisms that drive fibrogenesis may also contribute to fibrosis progression in alcoholic liver cirrhosis. We therefore tested whether C5 variants are associated with the stage of liver cirrhosis in these patients.

Methods

Patients with alcohol abuse and histology proven liver cirrhosis or unequivocal clinical signs of liver cirrhosis were included. Patients were genotyped for the two C5 htSNPs rs17611 and rs2300929 using fluorescent dye-marked reporter assays. Allele and genotype distribution were tested for an association with cirrhosis stage according to the Child-Pugh scoring system. Furthermore, we tested whether certain genotypes were independent risk factors for advanced liver cirrhosis (e.g. Child B/C versus Child A) via multiple logistic regression analysis.

Results

In total, 199 patients were included. Child status was available in 157 patients (Child A: 60; Child B: 47; Child C: 50). Overall allele frequencies for the rs17611 polymorphism were G-allele: 0.53; A-allele: 0.47 and for the rs2300929 polymorphism T-allele: 0.90; C-allele: 0.10. Carriage of the common allele of rs17611 was associated with Child A cirrhosis rather than Child B/C cirrhosis (OR=0.40; C.I.=0.169–0.967; p=0.038). No significant effect was detected for rs2300929. In logistic regression analysis, carriage of the common allele proved to be an independent protective factor for Child A cirrhosis (OR: 0.36; p=0.026).

Conclusion

The common allele of the htSNP rs17611 in the C5 gene is associated with milder stages of alcoholic liver cirrhosis, supporting the hypothesis that activation of the complement system contributes to fibrosis progression in end-stage alcoholic liver disease.