Genetic epidemiology of primary sclerosing cholangitis.
The aetiology of primary sclerosing cholangitis (PSC) is not known. A more than 80-fold increased risk of PSC among first-degree relatives emphasizes the importance of genetic factors. Genetic associations within the human leukocyte antigen (HLA) complex on chromosome 6p21 were detected in PSC 25 years ago. Subsequent studies have substantiated beyond doubt that one or more genetic variants located within this genetic region are important. The true identities of these variants, however, remain to be identified. Several candidate genes at other chromosomal loci have also been investigated. However, according to strict criteria for what may be denominated a susceptibility gene in complex diseases, no such gene exists for PSC today. This review summarises present knowledge on the genetic susceptibility to PSC, as well as genetic associations with disease progression and clinical subsets of particular interest (inflammatory bowel disease and cholangiocarcinoma).
Karlsen
Tom-H
TH
Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway. t.h.karlsen@klinmed.uio.no
Schrumpf
Erik
E
Boberg
Kirsten-Muri
KM
D001650:Bile Duct Neoplasms / Q000235:genetics / Q000276:immunology; D001653:Bile Ducts, Intrahepatic / Q000276:immunology; D018281:Cholangiocarcinoma / Q000235:genetics / Q000276:immunology; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D002896:Chromosomes, Human, Pair 6; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D015987:Effect Modifier, Epidemiologic; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology; D016017:Odds Ratio; D010375:Pedigree; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors
D006680:HLA Antigens