title: The sex-dependent role of the glucocorticoid receptor in depression: variations in the NR3C1 gene are associated with major depressive disorder in women but not in men.
abstract: Genetic variations in the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) have been associated with maladaptive stress responses and major depressive disorder (MDD). In a case-control study design, we examined whether single nucleotide polymorphisms (SNPs) and haploid genotype (haplotype) associations of MR gene NR3C2, GR gene NR3C1 and genes of GR chaperone molecules FK506 binding protein 5 (FKBP5) and corticotrophin-releasing hormone receptor 1 (CRHR1) differed between healthy subjects (n = 634) and inpatients with major depressive disorder (n = 412). All analyses were conducted for women and men separately. After conservative correction of Type-I-error to obtain reliable p values, one SNP in the NR3C1 gene, namely rs6195, showed a significant association with the presence of a major depression (p = 0.048) in females. In contrast, NR3C2, FKBP5 and CRHR1 polymorphisms were not significantly associated with MDD. No haplotype effects could be identified. Our results support the notion of an association between variants of GR-related genes in women and the pathophysiology of depression: females suffering from MDD showed a more than three times higher frequency of the T/C polymorphism compared to controls, which thus seems to increase the vulnerability to depression in females.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336, Munich, Germany. nina.sarubin@med.uni-muenchen.de.|Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University Munich, Munich, Germany. nina.sarubin@med.uni-muenchen.de.|Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany. nina.sarubin@med.uni-muenchen.de.|Hochschule Fresenius, University of Applied Sciences, Munich, Germany. nina.sarubin@med.uni-muenchen.de.
authors.forename: Nina
authors.initials: N
authors.lastname: Sarubin
authors.affiliation: Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University Munich, Munich, Germany.|Faculty of Psychology, Educational Science and Sport Science, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hilbert
authors.affiliation: Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Naumann
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Wimmer
authors.affiliation: Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Nothdurfter
authors.affiliation: Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
authors.affiliation: Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Baghai
authors.affiliation: Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bühner
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schüle
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012737:Sex Factors; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D000099052:CRF Receptor, Type 1; D000099159:Tacrolimus Binding Protein 5
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D022021:Tacrolimus Binding Proteins; D000099052:CRF Receptor, Type 1; D000099159:Tacrolimus Binding Protein 5; C497713:NR3C1 protein, human; C561839:NR3C2 protein, human
keywords: Depression; Genetic variations; HPA axis; NR3C1