Nature Genetics
37, 835 - 843 (2005)
Published online: 3 July 2005; | doi:10.1038/ng1599
Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humansSonja Hillebrandt1, 2, Hermann E Wasmuth1, Ralf Weiskirchen3, Claus Hellerbrand4, Hildegard Keppeler1, 2, Alexa Werth1, Ramin Schirin-Sokhan1, Gabriele Wilkens1, Andreas Geier1, Johann Lorenzen5, Jörg Köhl6, Axel M Gressner3, Siegfried Matern1
& Frank Lammert1, 21
Department of Medicine III, University Hospital Aachen, Aachen University, Aachen, Germany. 2
Department of Internal Medicine I, University Hospital Bonn, Bonner Forum Biomedizin, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. 3
Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Aachen, Aachen University, Aachen, Germany. 4
Department of Medicine I, University Hospital Regensburg, University of Regensburg, Regensburg, Germany. 5
Institute of Pathology, University Hospital Aachen, Aachen University, Aachen, Germany. 6
Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
Correspondence should be addressed to Frank Lammert frank.lammert@ukb.uni-bonn.de Fibrogenesis or scarring of the liver is a common consequence of all chronic liver diseases. Here we refine a quantitative trait locus that confers susceptibility to hepatic fibrosis by in silico mapping and show, using congenic mice and transgenesis with recombined artificial chromosomes, that the gene Hc (encoding complement factor C5) underlies this locus. Small molecule inhibitors of the C5a receptor had antifibrotic effects in vivo, and common haplotype-tagging polymorphisms of the human gene C5 were associated with advanced fibrosis in chronic hepatitis C virus infection. Thus, the mouse quantitative trait gene led to the identification of an unknown gene underlying human susceptibility to liver fibrosis, supporting the idea that C5 has a causal role in fibrogenesis across species.
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