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

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

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...

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Bibliographic Details
Published in:Nature genetics Vol. 37; no. 8; pp. 835 - 843
Main Authors: Lammert, Frank, Hillebrandt, Sonja, Wasmuth, Hermann E, Weiskirchen, Ralf, Hellerbrand, Claus, Keppeler, Hildegard, Werth, Alexa, Schirin-Sokhan, Ramin, Wilkens, Gabriele, Geier, Andreas, Lorenzen, Johann, Köhl, Jörg, Gressner, Axel M, Matern, Siegfried
Format: Journal Article
Language:English
Published: London Nature Publishing Group 01-08-2005
Subjects:
Animals
Biological and medical sciences
Chromosome Mapping
Chromosomes
Complement C5 - genetics
Complement C5 - metabolism
Diagnosis
Fundamental and applied biological sciences. Psychology
Gene mapping
Genetic aspects
Genetics of eukaryotes. Biological and molecular evolution
Genotype
Hepatitis
Hepatitis C virus
Humans
Liver
Liver Cirrhosis - genetics
Liver diseases
Methods
Mice
Mice, Inbred Strains
Physiological aspects
Polymorphism, Genetic
Quantitative Trait Loci
Risk factors
Germany
Human
Vertebrata
Mammalia
Gene
Mouse
Digestive system
Quantitative character
Liver
Rodentia
Complement
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Summary: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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ISSN:1061-4036
1546-1718
DOI:10.1038/ng1599