Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans.

Abstract

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.

• Authors: Sonja Hillebrandt, Hermann E Wasmuth, Ralf Weiskirchen, Claus Hellerbrand, Hildegard Keppeler, Alexa Werth, Ramin Schirin-Sokhan, Gabriele Wilkens, Andreas Geier, Johann Lorenzen, Jörg Köhl, Axel M Gressner, Siegfried Matern, Frank Lammert
• Journal: Nature genetics (Nat Genet) Vol. 37 Issue 8 Pg. 835-43 (Aug 2005) ISSN: 1061-4036 [Print] United States
• PMID: 15995705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Complement C5

Topics

• Animals
• Chromosome Mapping
• Complement C5 (genetics, metabolism)
• Genotype
• Humans
• Liver Cirrhosis (genetics)
• Mice
• Mice, Inbred Strains
• Polymorphism, Genetic
• Quantitative Trait Loci