Z Gastroenterol 2007; 45 - A1_14
DOI: 10.1055/s-2007-967768

Contribution of common variants in the complement factor H gene to fibrogenesis in chronic hepatitis C virus (HCV) infection

F Grünhage 1, H Keppeler 1, M Odenthal 2, U Drebber 2, HE Wasmuth 3, C Hellerbrand 4, HP Dienes 2, T Sauerbruch 1, F Lammert 5
  • 1Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn, Bonn
  • 2Institut für Pathologie der Universität zu Köln, Köln
  • 3Department of Internal Medicine III, RWTH Aachen, Aachen
  • 4Medizinische Klinik und Poliklinik I, Universität Regensburg, Regensburg
  • 5Medizinische Klinik und Poliklinik I, Universität Bonn, Bonn

Background

We recently showed that the complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis. We thus hypothesized that variations in other factors regulating the complement system might also influence fibrosis progression. Of note, common variants of the CFH gene encoding the complement inhibitor factor H have been identified as susceptibility loci for the development of age-related macular degeneration (Science 2005;308: 385–9), which displays histo-pathological characteristics of organ fibrosis like deposition of extracellular matrix proteins and progressive fibrotic tissue degeneration. Hence, we tested the association of alleles for age-related macular degeneration in the CFH gene (single nucleotide polymorphisms rs380390 and rs1061170 [Y402H] with liver fibrosis in patients with chronic hepatitis C virus (HCV) infection.

Patients and methods

Patients with chronic HCV infection were recruited at three university hospitals (Aachen, Cologne, Regensburg). Liver specimens were staged using the Desmet/Scheuer score and classified as mild fibrosis (stages 0–2) or severe fibrosis (stages 3–4). CFH polymorphisms were genotyped using fluorescent dye-marked reporter assays. Association tests were performed using the software package developed by Strom and Wienker (http: //ihg.gsf.de).

Results

A total of 467 patients were included in the study. Men were over-represented in our cohort (m: f 1.8: 1.0), and mean age was 42 years (range 13–84). Heterozygous carriers (n=197/467) of the rare allele of the rs380390 variant had an increased odds ratio (OR) for the development of severe fibrosis (OR=1.70; 95% CI=[1.03–2.88]; p=0.034). Multiple logistic regression analysis controlling for age and gender confirmed these results (OR=1.70; 95% CI=[1.05–2.76]; p=0.033). There was only a trend for an increased OR in carriers of the risk allele (p=0.062), probably due to the small number of homozygous patients (70/467). No association was detected for the CFH variant rs1061170.

Conclusion

In our cohorts, the CFH gene variant rs380390 and haplotypes without the Y402H coding variant were associated with advanced fibrosis stages. We propose that genetic variation in this regulator of the alternative complement pathway contributes to the complex individual predisposition to rapid progression of liver fibrosis.