Research article

Is FKBP5 a genetic marker of affective psychosis? A case control study and analysis of disease related traits

Micha Gawlik¹ , Kerstin Moller-Ehrlich¹ , Meinhard Mende² , Michael Jovnerovski¹ , Sven Jung³ , Burkhard Jabs¹ , Michael Knapp² and Gerald Stoeber¹

¹  Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstraße 15, 97080 Würzburg, Germany

²  Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany

³  Department of Forensic Medicine, University of Würzburg, Lindleinstraße 15, 97080 Würzburg, Germany

author email corresponding author email

BMC Psychiatry 2006, 6:52doi:10.1186/1471-244X-6-52

Published:	2 November 2006

Abstract

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.

Conclusion

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.