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Immunogenetics in PSC.

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.[1]

References

  1. Immunogenetics in PSC. Donaldson, P.T., Norris, S. Best practice & research. Clinical gastroenterology. (2001) [Pubmed]
 
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