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. Biological Psychiatry, 62, (8), 863-869. (doi:10.1016/j.biopsych.2007.04.013).
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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.
We investigated 206 healthy subjects and assessed associations between four common GR gene (NR3C1) polymorphisms (ER22/23EK, N363S, BclI, 9β) 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).
Male 9β 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 9β AG carriers had elevated ACTH levels (sex by genotype interaction p = .03).
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.
|Keywords:||glucocortcoid receptor gene polymorphism, glucocorticoid sensitivity, hypothalamus-pituitary-adrenal (hpa) axis, psychosocial stress|
|Subjects:||R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Q Science > QH Natural history > QH426 Genetics
B Philosophy. Psychology. Religion > BF Psychology
|Divisions:||University Structure - Pre August 2011 > School of Psychology
|Date Deposited:||06 Aug 2007|
|Last Modified:||01 Jun 2011 00:14|
|Contributors:||Kumsta, Robert (Author)
Entringer, Sonja (Author)
Koper, Jan W. (Author)
van Rossum, Elisabeth F.C. (Author)
Hellhammer, Dirk H. (Author)
Wüst, Stefan (Author)
|Date:||15 August 2007|
|Contact Email Address:||firstname.lastname@example.org|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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