title: Genetics of primary sclerosing cholangitis and pathophysiological implications.
abstract: Primary sclerosing cholangitis (PSC) is a chronic disease leading to fibrotic scarring of the intrahepatic and extrahepatic bile ducts, causing considerable morbidity and mortality via the development of cholestatic liver cirrhosis, concurrent IBD and a high risk of bile duct cancer. Expectations have been high that genetic studies would determine key factors in PSC pathogenesis to support the development of effective medical therapies. Through the application of genome-wide association studies, a large number of disease susceptibility genes have been identified. The overall genetic architecture of PSC shares features with both autoimmune diseases and IBD. Strong human leukocyte antigen gene associations, along with several susceptibility genes that are critically involved in T-cell function, support the involvement of adaptive immune responses in disease pathogenesis, and position PSC as an autoimmune disease. In this Review, we survey the developments that have led to these gene discoveries. We also elaborate relevant interpretations of individual gene findings in the context of established disease models in PSC, and propose relevant translational research efforts to pursue novel insights.
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Postbox 4950Nydalen, 0424 Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Postbox 1171 Blindern, 0318 Oslo, Norway.|Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Postbox 4950 Nydalen, 0424 Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Postbox 1171 Blindern, 0318 Oslo, Norway.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Postbox 4950Nydalen, 0424 Oslo, Norway.|Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Postbox 1171 Blindern, 0318 Oslo, Norway.|Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Postbox 4950 Nydalen, 0424 Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Postbox 1171 Blindern, 0318 Oslo, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
mesh_terms: D015209:Cholangitis, Sclerosing / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006801:Humans