PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11492971

Immunogenetics in PSC.

P T Donaldson·S Norris
View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

Cholangitis, SclerosingDisease SusceptibilityHumansMajor Histocompatibility ComplexJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P T Donaldson, S Norris. 2001. Immunogenetics in PSC.. https://doi.org/10.1053/bega.2001.0208

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2024

Network proximity analysis as a theoretical model for identifying potential novel therapies in primary sclerosing cholangitis.

Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with no licensed therapies. Previous Genome Wide Association Studies (GWAS) have identified genes that correlate significantly with PSC, and these were identified by systematic review. Here we use novel Network Proximity Analysis (NPA) methods to identify already licensed candidate drugs that may have an effect on the genetically coded aspects of PSC pathophysiology.Over 2000 agents were identified as significantly linked to genes implicated in PSC by this method. The most significant results include previously researched agents such as metronidazole, as well as biological agents such as basiliximab, abatacept and belatacept. This in silico analysis could potentially serve as a basis for developing novel clinical trials in this rare disease.

Cholangitis, Sclerosing↗
PubMed2003

The management of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic hepatobiliary disease that usually progresses to biliary cirrhosis and liver failure; it also predisposes to cholangiocarcinoma. The cause of PSC is unknown, although evidence suggests that the tissue damage is mediated by the immune system. There is an unexplained close association between PSC and inflammatory bowel disease, particularly in ulcerative colitis, which coexists in the majority of patients with PSC. No medical therapy has been proven to halt or reverse disease progression; however, recent preliminary evidence suggests that ursodeoxycholic acid (UDCA) in a high dose of 20 to 25 mg/kg may slow the disease process. Evidence from a pilot study suggests that the combination of UDCA and immunosuppressive therapy, such as prednisolone or azathioprine, may also increase efficacy. For patients with end-stage PSC, liver transplantation remains the only effective therapy, although there is clear evidence that PSC may recur in the liver allograft.

Cholangitis, Sclerosing↗