title: Genetic variants of the bile salt export pump: inducers and modifiers of liver diseases.
abstract: The bile salt export pump (BSEP, ABCB11) is the major transporter protein for the excretion of bile salts into bile. Here we describe a spectrum of BSEP-dependent effects on the course of liver diseases, and present two mutations that differentially affect total bile acid output and the biliary bile acid profile. According to the clinical course of affected children, low bile acid output but a normal profile was less harmful than higher output in combination with changes in the ratio of chenodeoxycholic acid to cholic acid. On the other hand, the common BSEP polymorphism V444A (c.1331T>C; allele frequency 65%) emerged as an independent predictor of the success rate in patients with chronic hepatitis C treated with pegylated interferon/ribavirin. This association between bile acid transport and hepatitis C may be due to interference of bile acids with viral replication, interferon signaling or antiviral proteins.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectiology, University Hospital Düsseldorf, Düsseldorf, Germany. kubitz@med.uni-duesseldorf.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Kubitz
authors.forename: Christoph
authors.initials: C
authors.lastname: Brinkmeyer
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Sagir
authors.forename: Diran
authors.initials: D
authors.lastname: Herebian
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008107:Liver Diseases / Q000235:genetics*; D008297:Male; D008958:Models, Molecular
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters