Study Report

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Basic Info

Reference	Szczepankiewicz, A.,2011 PMID: 21764460
Citation	Szczepankiewicz, A., A. Leszczynska-Rodziewicz, et al. (2011). "Glucocorticoid receptor polymorphism is associated with major depression and predominance of depression in the course of bipolar disorder." J Affect Disord 134(1-3): 138-144.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	514 patients with bipolar disorder, 193 patients with major depressive disorder and 732 healthy subjects
SNP/Region/Marker Size	8 SNPs
Predominant Ethnicity	Caucasian
Population	Polish
Gender	42.8% male in patients with bipolar disorder, 25.4% male in patients patients with major depressive disorder and 42.5% male in healthy subjects
Age Group	Adults : Mean age(SD)(year): 45.2(13.5)[31.6(11.5) at onset] in BD patients,44.9(13.8) [38.8(13.5) at onset] in MDD patients and 39.9(12.7) in controls

Detail Info

Sample Diagnosis	DSM
Sample Status	The study was performed on 707 patients with affective disorders: 514 patients with bipolar disorder (388 patients with bipolar disorder type I, 126 patients with bipolar disorder type II) and 193 patients with major depressive disorder. Patients were recruited from inpatients from Wielkopolska region, considered as ethnically homogenous (Cavalli-Sforza, 1994), treated at the Department of Psychiatry, University of Medical Sciences in Poznan. Consensus lifetime diagnosis by at least two experienced psychiatrists was made for each patient. The phenotyping of patients was based on clinical interviews, medical records and family history method according to DSM-IV criteria using SCID (Structured Clinical Interview for DSM Disorders) (First et al., 1996) that provide relevant information regarding the course of both disorders. The control group consisted of 732 subjects. Control subjects were recruited from the group of healthy volunteers, blood donors and hospital staff and students of University of Medical Sciences in Poznan and Clinical Neuropsychology Unit, Collegium Medicum Bydgoszcz. Only 40% of the control group was psychiatrically screened using the Polish version of M.I.N.I Plus scale (Lecrubier et al., 1997) for excluding presence of any serious mental health problems.
Technique	PCR and sequencing
Statistical Method	The two-tailed Pearson's chi-square test and Fisher's exact test were used to test differences in the genotypic and allelic (respectively) distribution between the groups of patients and control subjects.
Result Summary	RESULTS: We have found three polymorphisms (rs6198, rs6191 and rs33388) to be associated with major depressive disorder (MDD) and the same polymorphisms were associated with the predominance of depressive symptoms in the course of bipolar disorder. In linkage disequilibrium analysis we observed two haplotype blocks, however, none of those shows involvement in susceptibility to MDD or bipolar disorder. LIMITATIONS: The main limitation of this study is relatively small sample size of MDD patients group. CONCLUSIONS: Polymorphisms of NR3C1 gene analyzed in this study may modify susceptibility to major depressive disorder and seem to influence the course of bipolar disorder.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 7)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs258813	NR3C1	A/G	For BD, X² test: allele, P-value > 0.05; the Fisher exact test: genotype, P-value > 0.05; for the course of bipolar disorder: genotype P-value = 0.148	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6198	NR3C1	C/T	For BD, X² test: allele, P-value > 0.05; the Fisher exact test: genotype, P-value > 0.05; for the course of bipolar disorder: genotype P-value = 0.028	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs10052957	NR3C1	A/G	For BD, X² test: allele, P-value > 0.05; the Fisher exact test: genotype, P-value > 0.05; for the course of bipolar disorder: genotype P-value = 0.122	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6196	NR3C1	A/G	For BD, X² test: allele, P-value > 0.05; the Fisher exact test: genotype, P-value > 0.05; for the course of bipolar disorder: genotype P-value = 0.138	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs41423247	NR3C1	C/G	For BD, X² test: allele, P-value > 0.05; the Fisher exact test: genotype, P-value > 0.05; for the course of bipolar disorder: genotype P-value = 0.192	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6191	NR3C1	A/C	For BD, X² test: allele, P-value > 0.05; the Fisher exact test: genotype, P-value > 0.05; for the course of bipolar disorder: genotype P-value = 0.029	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs33388	NR3C1	A/T	For BD, X² test: allele, P-value > 0.05; the Fisher exact test: genotype, P-value > 0.05; for the course of bipolar disorder: genotype P-value = 0.050	No significant association was observed in BD. No significant association was observed in BD.	Negative

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs6195	NR3C1	point mutation	A/G		For BD, X² test:allele, P-value > 0.05;the Fisher exact test:genotype, P-value > 0.05;for the course of bipolar disorder:genotype P-value = 0.248	No significant association was observed in BD. No significant association was observed in BD.	Negative

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

Gene	Statistical Values/Author Comments	Result Category
NR3C1	Genotype and allele frequency distributions did not differ significantly between BD patients and con...... Genotype and allele frequency distributions did not differ significantly between BD patients and controls. More...	Negative

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
MDD	rs33388	NR3C1	X² test:allele, P-value = 0.018, OR=0.759, 95% CI=0.605-0.953;the Fisher exact test:genotype, P-value > 0.05	Significant association was found.	Positive
MDD	rs258813	NR3C1	X² test:allele, P-value > 0.05;the Fisher exact test:genotype, P-value > 0.05	No significant association was observed.	Negative
MDD	rs6191	NR3C1	X² test:allele, P-value = 0.015 for alleles, OR=1.338, 95% CI: 1.059-1.689;the Fisher exact test:genotype, P-value = 0.049	Significant association was found.	Positive
MDD	rs41423247	NR3C1	X² test:allele, P-value > 0.05;the Fisher exact test:genotype, P-value > 0.05	No significant association was observed.	Negative
MDD	rs10052957	NR3C1	X² test:allele, P-value > 0.05;the Fisher exact test:genotype, P-value > 0.05	No significant association was observed.	Negative
MDD	rs6198	NR3C1	X² test:allele, P-value > 0.05;the Fisher exact test:genotype, P-value = 0.018, df=2, X²=7.964, OR=0.950, 95% CI: 0.693-1.303.	Significant association was found.	Positive
MDD	rs6196	NR3C1	X² test:allele, P-value > 0.05;the Fisher exact test:genotype, P-value > 0.05	No significant association was observed.	Negative

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Description	Result Category
MDD	rs6195	NR3C1	point mutation	X² test:allele, P-value > 0.05;the Fisher exact test:genotype, P-value > 0.05	No significant association was observed.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
MDD	NR3C1	We have found three polymorphisms (rs6198, rs6191 and rs33388) to be associated with major depressive disorder (MDD)	Pos