title: Heterozygous Inactivation of the Nuclear Receptor PXR/NR1I2 in a Patient With Anabolic Steroid-Induced Intrahepatic Cholestasis.
abstract: BACKGROUND
  The incidence of liver damage due to steroid consumption is increasing due to the omnipresence of the idealized body image and the widespread availability of drugs via the Internet. The genetic factors underlying individual susceptibility are not presently known.
  
  
  METHODS
  A male patient developed cholestatic liver injury two weeks after a two-month course of anabolic steroids. Next-generation sequencing (NGS) of 24 cholestasis-related genes revealed a heterozygous two-basepair deletion in exon 1 of the pregnane X receptor gene (PXR). Serum bile salt levels showed marked imbalances, strongly resembling the changes observed in patients with biliary obstruction.
  
  
  CONCLUSIONS
  This case of PXR haploinsufficiency reveals transcriptional regulatory functions activated in the liver under xenobiotic stress by steroids, which appear to require two functional copies of the nuclear receptor gene. Deranged bile salt levels outline the central role of PXR in bile acid synthesis, modification, and export.
authors: Department of Medicine II, Saarland University, Homburg, Germany.
authors: Roman
authors: R
authors: Liebe
authors: Department of Medicine II, Saarland University, Homburg, Germany; Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors: Marcin
authors: M
authors: Krawczyk
authors: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors: Joanna
authors: J
authors: Raszeja-Wyszomirska
authors: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors: Beata
authors: B
authors: Kruk
authors: Gemeinschaftspraxis fur Humangenetik, Homburg, Germany.
authors: Rebecca
authors: R
authors: Preis
authors: CHU-Quebec, Research Center and the Faculty of Pharmacy, Laval University, Quebec, Canada.
authors: Jocelyn
authors: J
authors: Trottier
authors: CHU-Quebec, Research Center and the Faculty of Pharmacy, Laval University, Quebec, Canada.
authors: Olivier
authors: O
authors: Barbier
authors: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland; Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland.
authors: Piotr
authors: P
authors: Milkiewicz
authors: Department of Medicine II, Saarland University, Homburg, Germany.
authors: Frank
authors: F
authors: Lammert
keywords: Anabolic Steroids; Bile Acid Metabolism; Drug-Induced Cholestasis; Liver Disease; Nuclear Receptor PXR/NR1I2