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Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress.
Biol Psychiatry 2007; 62(8):863-9BP

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, 9beta) 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 9beta 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 9beta 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.

Authors+Show Affiliations

Department of Psychobiology, University of Trier, Trier, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17716631

Citation

Kumsta, Robert, et al. "Sex Specific Associations Between Common Glucocorticoid Receptor Gene Variants and Hypothalamus-pituitary-adrenal Axis Responses to Psychosocial Stress." Biological Psychiatry, vol. 62, no. 8, 2007, pp. 863-9.
Kumsta R, Entringer S, Koper JW, et al. Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. Biol Psychiatry. 2007;62(8):863-9.
Kumsta, R., Entringer, S., Koper, J. W., van Rossum, E. F., Hellhammer, D. H., & Wüst, S. (2007). Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. Biological Psychiatry, 62(8), pp. 863-9.
Kumsta R, et al. Sex Specific Associations Between Common Glucocorticoid Receptor Gene Variants and Hypothalamus-pituitary-adrenal Axis Responses to Psychosocial Stress. Biol Psychiatry. 2007 Oct 15;62(8):863-9. PubMed PMID: 17716631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. AU - Kumsta,Robert, AU - Entringer,Sonja, AU - Koper,Jan W, AU - van Rossum,Elisabeth F C, AU - Hellhammer,Dirk H, AU - Wüst,Stefan, Y1 - 2007/08/23/ PY - 2006/10/05/received PY - 2007/03/13/revised PY - 2007/04/05/accepted PY - 2007/8/25/pubmed PY - 2007/12/6/medline PY - 2007/8/25/entrez SP - 863 EP - 9 JF - Biological psychiatry JO - Biol. Psychiatry VL - 62 IS - 8 N2 - 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, 9beta) 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 9beta 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 9beta 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. SN - 0006-3223 UR - https://www.unboundmedicine.com/medline/citation/17716631/Sex_specific_associations_between_common_glucocorticoid_receptor_gene_variants_and_hypothalamus_pituitary_adrenal_axis_responses_to_psychosocial_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(07)00331-9 DB - PRIME DP - Unbound Medicine ER -