title: Effect of drug transporter pharmacogenetics on cholestasis.
abstract: BACKGROUND
  The liver is the central place for the metabolism of drugs and other xenobiotics. In the liver cell, oxidation and conjugation of compounds take place, and at the same time, bile formation helps in extrusion of these compounds via the biliary route. A large number of transporters are responsible for drug uptake into the liver cell and excretion into bile or efflux to the sinusoidal blood.
  
  
  METHODS
  Genetic variants of these transporters and their transactivators contribute to changes in drug handling and are also responsible for cholestatic syndromes of different severity. This review summarizes the current knowledge regarding the influence of these genetic changes. The review covers progressive hereditary cholestatic syndromes as well as recurrent or transient cholestatic syndromes such as drug-induced liver injury, intrahepatic cholestasis of pregnancy, and benign recurrent intrahepatic cholestasis.
  
  
  CONCLUSIONS
  Polymorphisms in transporter genes are frequent. For clinically relevant cholestatic syndromes, it often requires a combination of genetic variants or acquired triggers such as pregnancy or drug treatment. In combination with other pathogenetic aspects, genetic variants in drug transporters may contribute to our understanding of not only cholestatic diseases such as primary sclerosing cholangitis or primary biliary cirrhosis, but also the natural course of chronic liver disease in general.
authors.affiliation: Bethlehem Center of Health, Medical Clinic , Stolberg/Rhld , Germany.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Dietrich
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics; D002779:Cholestasis / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics / Q000503:physiopathology; D026901:Membrane Transport Proteins / Q000235:genetics*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010597:Pharmacogenetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000503:physiopathology
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations
keywords: bile salt transporter; drug-induced liver injury; gallstones; hereditary cholestasis; organic anion transporter; polymorphism