title: Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance.
abstract: Glucocorticoid resistance due to mutations in the gene for the glucocorticoid receptor has been suggested to be more common than is thought at present, owing to the relative mildness of its symptoms and the difficulty of its diagnosis. To investigate the prevalence of mutations in the glucocorticoid receptor gene responsible for relative insensitivity to glucocorticoids, we carried out polymerase chain reaction/single-strand conformation analysis of the glucocorticoid receptor gene in a group of 20, otherwise healthy, persons with a reduced response in a dexamethasone suppression test and in 20 controls. We did not find mutations or polymorphisms associated with a reduced sensitivity to glucocorticoids. However, we identified five novel polymorphisms in the gene for the human glucocorticoid receptor, which may be useful in analyzing whether loss of (part of) the glucocorticoid receptor gene plays a role in glucocorticoid-resistant malignancies. Although relative resistance to glucocorticoids seems to be rather frequent in otherwise healthy persons, it is not usually associated with mutations or polymorphisms in the glucocorticoid receptor gene.
authors.affiliation: Department of Internal Medicine III, Erasmus University Rotterdam, Dijkzigt University Hospital, The Netherlands. koper@inw3.fgg.eur.nl
authors.forename: J W
authors.initials: JW
authors.lastname: Koper
authors.forename: R P
authors.initials: RP
authors.lastname: Stolk
authors.forename: P
authors.initials: P
authors.lastname: de Lange
authors.forename: N A
authors.initials: NA
authors.lastname: Huizenga
authors.forename: G J
authors.initials: GJ
authors.lastname: Molijn
authors.forename: H A
authors.initials: HA
authors.lastname: Pols
authors.forename: D E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: M
authors.initials: M
authors.lastname: Karl
authors.forename: F H
authors.initials: FH
authors.lastname: de Jong
authors.forename: A O
authors.initials: AO
authors.lastname: Brinkmann
authors.forename: S W
authors.initials: SW
authors.lastname: Lamberts
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001794:Blood Pressure; D001824:Body Constitution; D015992:Body Mass Index; D002908:Chronic Disease; D003062:Codon; D004351:Drug Resistance / Q000235:genetics*; D005091:Exons; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012044:Regression Analysis; D012727:Sex Characteristics
chemical_list: D003062:Codon; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid