Evaluation of complement factor 5 variants as genetic risk factors for the development of advanced fibrosis in chronic hepatitis C infection q Juliane Halangk 1, * ,  , Christoph Sarrazin 2 , Konrad Neumann 3 , Gero Puhl 4 , Tobias Mueller 1 , Gerlinde Teuber 2 , Hartwig Klinker 5 , Holger Hinrichsen 6 , Peter Buggisch 7 , Olfert Landt 8 , Viola Weich 1 , Alexandra Bergk 1 , Bertram Wiedenmann 1 , Peter Neuhaus 4 , Thomas Berg 1, * ,à , Heiko Witt 1,à 1 Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charite ´ – Universita ¨ tsmedizin Berlin, Campus Virchow-Klinikum, Germany 2 Medizinische Klinik I, Klinikum der Johann-Wolfgang-Goethe-Universita ¨ t, Frankfurt/Main, Germany 3 Institut fu ¨ r Biometrie und Klinische Epidemiologie, Charite ´ Universita ¨ tsmedizin Berlin, Campus Mitte, Germany 4 Klinik fu ¨ r Allgemein, Viszeral und Transplantationschirurgie, Charite ´ Universita ¨ tsmedizin Berlin, Campus Virchow-Klinikum, Germany 5 Medizinische Klinik und Poliklinik II, Universita ¨t Wu ¨ rzburg, Germany 6 Gemeinschaftspraxis fu ¨ r Innere Medizin, Kiel, Germany 7 I. Medizinische Klinik, Universita ¨ tsklinikum Hamburg-Eppendorf, Germany 8 TIB MOLBIOL, Berlin, Germany 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. Ó 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Keywords: Cirrhosis; Liver transplantation; Viral hepatitis; Liver biopsy; APRI score 0168-8278/$34.00 Ó 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2008.05.021 Received 14 December 2007; received in revised form 24 April 2008; accepted 27 May 2008; available online 23 June 2008 Associate Editor: G.K.K. Lau q 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. * Corresponding authors. Tel.: +49 30 450 553072; fax: +49 30 450 553903. E-mail addresses: thomas.berg@charite.de (T. Berg), heiko.witt@charite.de (H. Witt).   Medizinische Klinik I, Markus-Krankenhaus, Frankfurt/Main, Germany. à Authors contributed equally to this work and share senior and corresponding authorship. Abbreviations: C5, complement factor 5; SNP, single nucleotide polymorphism; FRET, fluorescence resonance energy transfer; APRI, aspartate aminotransferase-to-platelet ratio index. www.elsevier.com/locate/jhep Journal of Hepatology 49 (2008) 339–345