Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress

Kumsta, Robert, Entringer, Sonja, Koper, Jan W., van Rossum, Elisabeth F.C., Hellhammer, Dirk H. and Wüst, Stefan (2007) Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. The World Journal of Biological Psychiatry, 62 (8), 863-869. (doi:10.1016/j.biopsych.2007.04.013).

Abstract

Background
Alterations in glucocorticoid (GC) signaling have been associated with a number of psychiatric disorders. Genetic variation of the glucocorticoid receptor (GR) might be one of the factors underlying susceptibility to stress related disease. Methods
We investigated 206 healthy subjects and assessed associations between four common GR gene (NR3C1) polymorphisms (ER22/23EK, N363S, BclI, 9?) and hypothalamic-pituitary-adrenal (HPA) axis responses to psychosocial stress (Trier Social Stress Test, TSST) and glucocorticoid sensitivity measured by a dexamethasone suppression test (DST). Results
Male 9? AG carriers displayed the highest adrenocorticotropic hormone (ACTH) and total cortisol TSST responses (for ACTH: main effect genotype p = .02) whereas male BclI GG carriers showed diminished responses. Remarkably, the BclI GG genotype in women (all using oral contraceptives) was associated with the highest total cortisol TSST responses, resulting in a significant sex by genotype interaction (p = .03). Following the DST, male 9? AG carriers had elevated ACTH levels (sex by genotype interaction p = .03). Conclusions
We observed significant sex specific associations between GR gene polymorphisms and HPA axis responses to psychosocial stress as well as GC sensitivity. These findings support the relevance of GR gene polymorphisms in HPA axis regulation. Genetic variations of the GR might constitute a risk factor in development of HPA axis related disorders.

This record has no associated files available for download.

Contributors

Download statistics