BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Study Report

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Basic Info

Reference	Spijker, A. T.,2009 PMID: 19133972
Citation	Spijker, A. T., E. F. van Rossum, et al. (2009). Functional polymorphism of the glucocorticoid receptor gene associates with mania and hypomania in bipolar disorder. Bipolar Disord 11(1): 95-101.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	241 Bipolar patients(198 Bipolar disorder type I patients,41 Bipolar disorder type II patients,2 Bipolar disorder not otherwise specified patients) and 532 controls
SNP/Region/Marker Size	6 SNPs
Predominant Ethnicity	Caucasian
Population	Dutch
Gender	Gender(% male): 102(42) in BD patients, 285(54) in control
Age Group	Adults : Mean age(SD)(year):47.8(10.8) in cases and 42.7(12.2) in controls

Detail Info

Sample Diagnosis	DSM
Sample Status	Patients with BD type I, BD type II, and BD not otherwise specified, according to DSM-IV criteria, were included. The design of the study was approved by the independent Dutch national medical ethics committee. All patients treated in the outpatient Clinic for Mood Disorders in The Hague were invited to participate. All 412 patients being treated for BD by the Outpatient Clinic for Mood Disorders in The Hague (The Netherlands) were invited to participate in the study, either by letter or directly by their treating physician. After written informed consent was obtained, 245 patients were enrolled. To assess the diagnosis and comorbidity according to the DSM-IV criteria, patients were interviewed by trained research assistants using the Mini International Neuropsychiatric Interview Plus (MINI) (18). Sociodemographic and ethnic data were collected, and the Questionnaire for Bipolar Illness, Dutch translation (QBP-NL;Akkerhuis, Groenesteyn, Nolen 1997) was used to specify subtypes of BD and its course over time.Age of onset (years), mean(SD) First depressive episode 25(11.6),First (hypo)manic episode 29(11.7);Depressive episodes:Mean number(SD) 15(22.0),Median 6; Manic episodes:Mean number(SD) 12(19.9),Median 5;Interepisode functioning, n (%): 142 (58.9) Well functioning ;61 (25.4) Some problems, most of the time well functioning;16 (6.6) Severely disturbed;22 (9.1) No difference between episodes;Use of medication, n (%) :203 (84) Lithium,31 (13) Valproate,8 (3) Carbamazepine,11 (5) Lamotrigine,71 (30) Antidepressants;Comorbidity, n (%):108 (47)>= comorbid disorders,91 (39) Anxiety disorder,10 (4) Somatoform disorder,9 (4) Pain disorder,6 (3) Bulimia nervosa,5 (2) Drug dependency,12 (5) Alcohol dependency,6 (3) Attention-deficit hyperactivity disorder,15 (11) Of all women have premenstrual dysphoria.Blood samples from 532 healthy control subjects were randomly collected from the Rotterdam blood donation bank. Only the gender and age of these subjects are known.
Technique	genotyping
Statistical Method	Data were analyzed using SPSS [release 12.0.1 for Windows (SPSS, Chicago, IL, USA)]. Analyses for binary outcomes (case-control and dichotomous response variables) were performed with logistic regression analysis.
Result Summary	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.

SNPs reported by this study for BD (count: 2)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs6198	NR3C1	A/G		Genotypic association: OR = 0.76, 95% CI: 0.5-1.0, P-value = 0.14, corrected for age and gender; for age: OR = 1.04, 95% CI: 1.02-1.05, P-value = 0.000; for male gender: OR = 0.52, 95% CI: 0.37-0.72, P-value < 0.0001	We found a nonsignificant trend for a lower frequency of the...... We found a nonsignificant trend for a lower frequency of the A ?G or G ?G variation in exon 9beta in the patient group versus the control group. More...	Negative
rs10052957	NR3C1	C/T		Genotypic association: P-value = 0.03; odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.27-0.95	In subjects of the patient group, a significantly lower freq...... In subjects of the patient group, a significantly lower frequency of heterozygous TthIIII carriers compared to the control group was found More...	Positive

Genes reported by this study for BD (count: 1)