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 glucocorticoicl receptor (GR) gene Bell polymorphism. Methods: A total of 229 male subjects were classified into three Bell 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 clone, where the dependent variable was the clexamethasone-inclucecl cortisol suppression, and predictors included receptor variables. The interactions of the count of Gs 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. Limitations: 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. Conclusion: 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., (C) 2014 Elsevier By. All rights reserved.