title: Nuclear receptor variants in liver disease.
abstract: This snapshot reviews the current state of knowledge on genetic variants of nuclear receptors (NRs) involved in regulating various aspects of liver metabolism. Interindividual differences in responses to diet and other 'in-' and environmental stressors can be caused by variants in components of the NR regulatory gene network. We recapitulate recent evidence for the application of NRs in genetic diagnosis of monogenic liver disease. Genetic analysis of multifactorial liver diseases, such as nonalcoholic fatty liver disease and diabetes mellitus, pinpoints key players in disease predisposition and progression. In particular, NR1H4 variants have been associated with intrahepatic cholestasis of pregnancy and gallstone disease. Other examples include studies of NR1I2 and NR1I3 polymorphisms in patients with drug-induced liver injury and NR5A2 variation in cholangiocarcinoma. Associations of NR gene variants have been identified in patients with dyslipidemia and other metabolic syndrome-associated traits by genome-wide studies. Evidence from these analyses confirms a role for NR variation in common diseases, linking regulatory networks to complex and variable phenotypes. These new insights into the impact of NR variants offer perspectives for their future use in diagnosis and treatment of common diseases.
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zimmer
authors.forename: Roman
authors.initials: R
authors.lastname: Liebe
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
mesh_terms: D000090702:Constitutive Androstane Receptor; D055106:Genome-Wide Association Study; D006801:Humans; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000090702:Constitutive Androstane Receptor; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D000099150:Receptor, Farnesoid X-Activated; C000625852:NR1I2 protein, human; C000716327:NR1I3 protein, human; C082631:NR5A2 protein, human