Evaluation of complement factor 5 variants as genetic risk factors for the development of advanced fibrosis in chronic hepatitis C infection☆

Received 14 December 2007; received in revised form 24 April 2008; accepted 27 May 2008. published online 25 June 2008.

Background/Aims

Intercross studies in inbred mice susceptible or resistant to liver fibrosis revealed complement factor 5 as a quantitative trait gene associated with the development of fibrosis. In 277 patients with hepatitis C, two C5 SNPs, rs17611 and rs2300929, have been associated with advanced fibrosis.

Methods

We investigated the association of these C5 SNPs with advanced fibrosis in 1435 HCV infected patients and in 1003 patients with other liver diseases. We performed genotyping with melting curve analysis using fluorescence resonance energy transfer probes in the LightCycler.

Results

The defined high-risk genotypes (AA and TT) and alleles (A and T) were not associated with advanced fibrosis in HCV patients when Chi square testing and logistic regression analysis were applied (rs17611A 0.45 in F0-1 vs. 0.43 in F2-4, P=0.31; rs2300929T 0.91 F0-1 and 0.91 in F2-4, P=0.82). In the group of patients with liver diseases other than HCV we neither found an association of the C5 SNPs with advanced fibrosis nor an overrepresentation of the SNPs in patients with cirrhosis.

Conclusions

We found no evidence that these C5 SNPs are genetic risk factors for the development of advanced fibrosis in chronic HCV infection or other chronic liver diseases.

Associate Editor: G.K.K. Lau

Keywords: Cirrhosis, Liver transplantation, Viral hepatitis, Liver biopsy, APRI score

Abbreviations: C5, complement factor 5, SNP, single nucleotide polymorphism, FRET, fluorescence resonance energy transfer, APRI, aspartate aminotransferase-to-platelet ratio index

1 Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany

2 Medizinische Klinik I, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany

3 Institut für Biometrie und Klinische Epidemiologie, Charité Universitätsmedizin Berlin, Campus Mitte, Germany

4 Klinik für Allgemein, Viszeral und Transplantationschirurgie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany

5 Medizinische Klinik und Poliklinik II, Universität Würzburg, Germany

6 Gemeinschaftspraxis für Innere Medizin, Kiel, Germany

7 I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Germany

8 TIB MOLBIOL, Berlin, Germany

Corresponding authors. Tel.: +49 30 450 553072; fax: +49 30 450 553903.

☆ Dr. Landt is employed by TIB MOLBIOL, Berlin, Germany. The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.

† Medizinische Klinik I, Markus-Krankenhaus, Frankfurt/Main, Germany.

‡ Authors contributed equally to this work and share senior and corresponding authorship.

PII: S0168-8278(08)00371-1

doi:10.1016/j.jhep.2008.05.021

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