Journal of Hepatology
Volume 49, Issue 3 , Pages 339-345, September 2008

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

  • Juliane Halangk

      Affiliations

    • Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany
    • Corresponding Author InformationCorresponding authors. Tel.: +49 30 450 553072; fax: +49 30 450 553903.
    • Medizinische Klinik I, Markus-Krankenhaus, Frankfurt/Main, Germany.
    • ,
  • Christoph Sarrazin

      Affiliations

    • Medizinische Klinik I, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany
    • ,
  • Konrad Neumann

      Affiliations

    • Institut für Biometrie und Klinische Epidemiologie, Charité Universitätsmedizin Berlin, Campus Mitte, Germany
    • ,
  • Gero Puhl

      Affiliations

    • Klinik für Allgemein, Viszeral und Transplantationschirurgie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany
    • ,
  • Tobias Mueller

      Affiliations

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

      Affiliations

    • Medizinische Klinik I, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany
    • ,
  • Hartwig Klinker

      Affiliations

    • Medizinische Klinik und Poliklinik II, Universität Würzburg, Germany
    • ,
  • Holger Hinrichsen

      Affiliations

    • Gemeinschaftspraxis für Innere Medizin, Kiel, Germany
    • ,
  • Peter Buggisch

      Affiliations

    • I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Germany
    • ,
  • Olfert Landt

      Affiliations

    • TIB MOLBIOL, Berlin, Germany
    • ,
  • Viola Weich

      Affiliations

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

      Affiliations

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

      Affiliations

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

      Affiliations

    • Klinik für Allgemein, Viszeral und Transplantationschirurgie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany
    • ,
  • Thomas Berg

      Affiliations

    • Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany
    • Corresponding Author InformationCorresponding authors. Tel.: +49 30 450 553072; fax: +49 30 450 553903.
    • Authors contributed equally to this work and share senior and corresponding authorship.
    • ,
  • Heiko Witt

      Affiliations

    • Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany
    • Authors contributed equally to this work and share senior and corresponding authorship.

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

Associate Editor: G.K.K. Lau

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.

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

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☆ 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.

PII: S0168-8278(08)00371-1

doi:10.1016/j.jhep.2008.05.021

Journal of Hepatology
Volume 49, Issue 3 , Pages 339-345, September 2008

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