Related Experiment Video
Updated: Jul 17, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Polymorphisms in the steroid and xenobiotic receptor gene influence survival in primary sclerosing cholangitis
Tom H Karlsen1, Benedicte A Lie, Kathrine Frey Frøslie
1Medical Department, Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway. t.h.karlsen@klinmed.uio.no
Background & Aims:
The steroid and xenobiotic receptor (SXR) is a ligand-dependent transcription factor that mediates protection against bile acid-induced liver injury in cholestatic animal models. Ursodeoxycholic acid and rifampicin are known ligands. We investigated whether functional polymorphisms of the SXR gene influence disease susceptibility or disease progression in patients with primary sclerosing cholangitis (PSC).
Methods:
Polymorphisms at 8 loci across the SXR gene were genotyped in 327 Scandinavian PSC patients and 275 healthy controls. Kaplan-Meier survival analyses and Cox regressions were performed to estimate effects from genotypes on patient survival, defined as time from diagnostic cholangiography to death or liver transplantation.
Results:
Susceptibility to PSC was not associated with any of the SXR polymorphisms studied. Median survival was significantly reduced in patients homozygous for the minor allele as compared with patients carrying at least 1 major allele of the neighboring polymorphisms rs6785049 (10.8 vs 14.0 years, respectively, P = .01), rs1054190 (3.6 vs 13.6 years, respectively, P = .004), and rs3814058 (3.5 vs 13.3 years, respectively, P = .01). The increased risk of death or liver transplantation was confirmed in univariate Cox regressions (relative risk [RR](rs6785049) = 1.7, 95% CI: 1.1-2.6; RR(rs1054190) = 3.1, 95% CI: 1.4-7.1; and RR(rs3814058) = 2.2, 95% CI: 1.2-4.2 for the 3 polymorphisms, respectively). In multiple Cox regressions including age at PSC onset, rs1054190 remained an independent risk factor.
Conclusions:
Functional SXR gene variants appear to modify disease course in PSC. Further investigations of polymorphisms in the SXR gene may provide insight into the prognostic importance of SXR-regulated pathways in this disease, perhaps even in a therapeutic perspective.
More Related Videos
06:21Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
10:21Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification
Published on: September 20, 2024
Related Concept Videos
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenomics: Identification of New Drug Targets