ausblenden:
Schlagwörter:
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Zusammenfassung:
BACKGROUND: Polymorphisms in the FK506 binding protein 5 (FKBP5) gene
have been shown to influence glucocorticoid receptor sensitivity, stress
response regulation, and depression risk in traumatized subjects, with
most consistent findings reported for the functional variant rs1360780.
In the present study, we investigated whether the FKBP5 polymorphism
rs1360780 and lifetime history of major depression are associated with
DNA methylation and FKBP5 gene expression after psychosocial stress.
METHODS: A total of 116 individuals with a positive (n = 61) and
negative (n = 55) lifetime history of major depression participated in
the Trier Social Stress Test. We assessed plasma cortisol
concentrations, FKBP5 mRNA expression, and CpG methylation of FKBP5
intron 7 in peripheral blood cells.
RESULTS: Genotype-dependent plasma cortisol response to psychosocial
stress exposure was observed in healthy controls, with the highest and
longest-lasting cortisol increase in subjects with the TT genotype of
the FKBP5 polymorphism rs1360780, and healthy controls carrying the T
risk allele responded with a blunted FKBP5 mRNA expression after
psychosocial stress. No genotype effects could be found in remitted
depression.
CONCLUSIONS: The FKBP5 rs1360780 polymorphism is associated with plasma
cortisol and FKBP5 mRNA expression after psychosocial stress in healthy
controls but not in remitted depression. Preliminary results of the DNA
methylation analysis suggest that epigenetic modifications could be
involved.
