Within- and Inter- gene interactions in FKBP5 and GR genes and its association with early response

The glucocorticoid receptor (GR) is a member of the nuclear hormone receptor superfamily localized in the cytoplasm. Inactive GR is bound to a large protein complex that includes heat shock protein 90 (Hsp90). When glucocorticoids (GC) binds to GR, Hsp90 dissociates and the GC/GR complex translocates to the nucleus where it binds to specific palindromic sequences, termed glucocorticoid response elements (GREs), resulting in the transcription upregulation of various genes, one of them being FKBP5. In our study we used 375 patients with depressive disorder. We genotyped 52 SNPs in FKBP5.Two of the genotyped SNPs fell into GRE sequences and showed an association with early response to antidepressant treatment. We tested interactions between these two SNPs and one exonic SNP in the GR gene, which affects the transcription activity of GR-m-RNA. Significant statistical interaction between pairs of SNPs in FKBP5 and GR was detected. This could point to a polymorphisms-dependent functionality of GREs in the FKBP5 gene and its association with early response to antidepressant treatment.