Functional polymorphism of the glucocorticoid receptor gene associates with mania and hypomania in bipolar disorder.
OBJECTIVE
In affective disorders, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is a frequently observed phenomenon. Subtle changes in glucocorticoid receptor (GR) functioning caused by polymorphisms of the GR gene (NR3C1) may be at the base of the altered reaction of the HPA axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD).


METHODS
In this study, 245 patients with BD were interviewed to confirm diagnosis and BD subtype. Data on medication use and sociodemographic details were also collected. The control group consisted of 532 healthy blood donors, from which data on sex and age were collected. To perform genotyping, blood was collected from all patients and healthy controls.


RESULTS
A trend was found for a protective effect of the exon 9beta polymorphism (p = 0.14) and the TthIIII polymorphism (p < 0.05) on the manifestation of the disease. These effects were significantly influenced by male gender for both polymorphisms. Patients with BD and the A/G variant in exon 9beta had significantly fewer manic and hypomanic episodes than noncarriers (p < 0.05). No further associations were found with the other investigated GR gene polymorphisms and BD. These findings were not corrected for multiple comparisons.


CONCLUSIONS
We conclude that the exon 9beta polymorphism and the TthIIII polymorphism of the GR gene may be associated with a protective effect on the clinical manifestation and course in patients with BD. Furthermore, no associations were found between the other studied GR gene polymorphisms and this disease.
Spijker
Anne T
AT
Parnassia BAVO Group, The Hague.
van Rossum
Elisabeth F C
EF
Hoencamp
Erik
E
DeRijk
Roel H
RH
Haffmans
Judith
J
Blom
Marc
M
Manenschijn
Laura
L
Koper
Jan W
JW
Lamberts
Steven Wj
SW
Zitman
Frans G
FG
D000328:Adult; D001714:Bipolar Disorder / Q000145:classification* / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*
C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid