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Semin Liver Dis 2011; 31(2): 188-207
DOI: 10.1055/s-0031-1276647
© Thieme Medical Publishers

Deciphering the Genetic Predisposition to Primary Sclerosing Cholangitis

Tom H. Karlsen1 , Arthur Kaser2 , 3
  • 1Norwegian PSC Research Center, Clinic for Specialized Surgery and Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  • 2Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
  • 3Department of Medicine II, Innsbruck Medical University, Innsbruck, Austria
Further Information

Publication History

Publication Date:
02 May 2011 (online)

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ABSTRACT

Genetic variants within the major histocompatibility complex (MHC) on chromosome 6 have been shown to confer risk for primary sclerosing cholangitis (PSC) ~30 years ago. However, robust genetic associations outside this genetic region have been difficult to establish. By genome-wide association analysis, a surprising large overlap of genetic risk loci outside of the MHC with prototypical autoimmune diseases has been recognized. In this article, we review the present knowledge of susceptibility loci in PSC, by assessing the robustness of the findings and speculating on potential mechanistic roles of predicted risk genes in PSC pathogenesis. We suggest a model where the primary insult is likely to resemble the tissue injury in most autoimmune conditions. Functional insight into risk pathways could offer novel therapeutic opportunities, and we speculate on specific opportunities that may arise based on current knowledge.

KEYWORDS

Primary sclerosing cholangitis - genetic predisposition - comorbidities - T lymphocytes - major histocompatibility complex

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Arthur KaserM.D. 

Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke's Hospital

Hills Road, Cambridge CB2 0QQ, United Kingdom

Email: ak729@cam.ac.uk