Is FKBP5 a genetic marker of affective psychosis? A case control study and analysis of disease related traits.
BACKGROUND
A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an important pathogenic factor in depression. Genetic variants of FKBP5, a protein of the HPA system modulating the glucocorticoid receptor, have been reported to be genetically associated with improved response to medical treatment and an increase of depressive episodes.


METHODS
We examined three single nucleotide polymorphisms (SNPs) in FKBP5, rs4713916 in the proposed promoter region, rs1360780 in the second intron and rs3800373 in the 3'-untranslated region (3'-UTR), in a case-control study of Caucasian origin (affective psychosis: n = 248; controls: n = 188) for genetic association and association with disease related traits.


RESULTS
Allele and genotype frequencies of rs4713916, rs1360780 and rs3800373 were not significantly different between cases and controls. Two three-locus haplotypes, G-C-T and A-T-G, accounted for 86.2% in controls. Odds ratios were not increased between cases and controls, except the rare haplotype G-C-G (OR 6.81), representing 2.1% of cases and 0.3% of controls. The frequency of rs4713916AG in patients deviated from expected Hardy-Weinberg equilibrium, the genotype AA at rs4713916 in monopolar depression (P = 0.011), and the two-locus haplotype rs1360780T--rs3800373T in the total sample (overall P = 0.045) were nominally associated with longer continuance of disease.


CONCLUSIONS
Our data do not support a significant genetic contribution of FKBP5 polymorphisms and haplotypes to affective psychosis, and the findings are inconclusive regarding their contribution to disease-related traits.
Gawlik
Micha
M
Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. gawlik_m@klinik.uni-wuerzburg.de
Moller-Ehrlich
Kerstin
K
Mende
Meinhard
M
Jovnerovski
Michael
M
Jung
Sven
S
Jabs
Burkhard
B
Knapp
Michael
M
Stoeber
Gerald
G
D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000235:genetics* / Q000523:psychology; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
D005819:Genetic Markers; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5