Immunogenetics in PSC

Best Pract Res Clin Gastroenterol. 2001 Aug;15(4):611-27. doi: 10.1053/bega.2001.0208.


Primary sclerosing cholangitis (PSC) does not exhibit simple Mendelian inheritance attributable to a single gene locus and our knowledge of the genetics of this complex disease is based entirely on case-control studies of candidate genes. The prime candidates in PSC are inherited variation (polymorphism) in the genes that regulate the immune response, especially the genes of the major histocompatability complex (MHC). Thus far, five different human leukocyte antigen (HLA) haplotypes have been associated with PSC: three with increased risk of disease and two with reduced risk. More recently studies of non-MHC genes have failed to associate PSC with several cytokine genes (IL-1 and IL-10), with FAS (TNFRSF6), with TGFbeta-1, or with CCR-5 but have found genetic links with MMP-3 and disease progression, whilst the potential role of CTLA-4 gene polymorphism remains in question. With the completion of the human genome project, understanding the genetics of complex (non-Mendelian) disease is a major priority for the research community and the studies summarized herein may guide these future investigations.

Publication types

  • Review

MeSH terms

  • Cholangitis, Sclerosing / genetics*
  • Cholangitis, Sclerosing / immunology
  • Disease Susceptibility
  • Humans
  • Major Histocompatibility Complex / immunology