title: GR gene BclI polymorphysm changes the path, but not the level, of dexamethasone-induced cortisol suppression.
abstract: BACKGROUND
  The hypothalamo-pituitary-adrenocortical (HPA) axis self-regulation is achieved via cortisol binding to mineralocorticoid (MR) and glucocorticoid receptors (GR). It is often disturbed in mental disorders, particularly in those where traumatic stress has been implicated, such as posttraumatic stress disorder and depression. Although dexamethasone suppression test (DST) is often used as diagnostic aid, the findings still vary. In search of the factors influencing the DST outcome, we examined the glucocorticoid receptor (GR) gene BclI polymorphism.
  
  
  METHODS
  A total of 229 male subjects were classified into three BclI groups: two groups with homozygous carriers (of the G allele, N=108, and of the C allele, N=26), and one with heterozygous carriers (N=95). Multiple hierarchical linear regression analysis was done, where the dependent variable was the dexamethasone-induced cortisol suppression, and predictors included receptor variables. The interactions of the count of 'G׳s with the predictors were introduced to single out the effects of the G allele.
  
  
  RESULTS
  The means of all studied variables, including suppression, are statistically the same in the three groups. However, the mechanism of suppression involves MRs only in the G allele carriers.
  
  
  CONCLUSIONS
  The subjects were selected by criteria suited for the aim of the large project whose part is this study, hence the relatively small number of CC carriers. Also, we did not assess MR functional properties that would probably sharpen the results.
  
  
  CONCLUSIONS
  Our finding that MRs participate in cortisol suppression in the G allele carriers suggests that research aimed at refining HPA axis-based therapy might require its adjustment for such patients.
authors.affiliation: Vinca Institute, Laboratory for Theoretical and Condensed Matter Physics 020/2, University of Belgrade, PO Box 522, 11001 Belgrade, Serbia. Electronic address: danka.s@sbb.rs.
authors.forename: Danka
authors.initials: D
authors.lastname: Savic
authors.affiliation: University of Belgrade, Faculty of Philosophy, School of Psychology, Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Knezevic
authors.affiliation: Institute of Endocrinology, Diabetes and Metabolic Disease, University of Belgrade, Belgrade, Serbia.
authors.forename: Svetozar
authors.initials: S
authors.lastname: Damjanovic
authors.affiliation: Institute of Endocrinology, Diabetes and Metabolic Disease, University of Belgrade, Belgrade, Serbia.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Antic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Matic
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003907:Dexamethasone / Q000494:pharmacology*; D005787:Gene Frequency; D005938:Glucocorticoids / Q000494:pharmacology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D055771:Serbia; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone
keywords: Dexamethasone suppression test; GR gene snp BclI; Glucocorticoid receptor; Mineralocorticoid receptor