The relationship between childhood trauma, rs1360780 genotypes, FKBP5 intron 7 methylation and posttraumatic stress disorder in women who have experienced rape.

Background

Posttraumatic stress disorder (PTSD) is a common sequela of rape. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, a core regulator of the stress response, has been implicated in the aetiology and chronicity of PTSD. FK506 binding protein (FKBP5) is a co-chaperone and functional regulator of the glucocorticoid receptor and the HPA-axis.

Objective

This study investigated main and interaction effects of childhood trauma and the FKBP5 rs1360780 genotype on longitudinal FKBP5 intron 7 methylation, and whether change in FKBP5 methylation over time was associated with PTSD symptom severity over time.Method: Women who experienced rape (n = 96) were recruited from post-rape care services in KwaZulu Natal, South Africa. Total PTSD symptom scores, derived from the Davidson Trauma Scale, were assessed at baseline, 3-months and 6-months post-rape. Methylation levels at five FKBP5 intron 7 CpG sites were determined using EpiTYPER Sequenom MassArray technology. Genotyping of rs1360980 was completed using the Agena MassArray genotyping system. Mixed linear regression models were used to analyse the data.

Results

The interaction between rs1360780 genotype and childhood trauma was a significant predictor of FKBP5 methylation over time. There was a significant positive correlation between childhood trauma and methylation levels in participants with the CT and TT genotypes, while there was a significant negative correlation between childhood trauma and methylation in CC genotype carriers. FKBP5 methylation was not a predictor of PTSD scores over time.

Conclusion

This is the first study to investigate longitudinal change in FKBP5 methylation in a demographically homogenous same-trauma sample. The findings implicate childhood trauma and FKBP5 rs1360980 genotype in the trajectory of FKBP5 methylation levels in the aftermath of rape. Further research is needed to investigate the longitudinal role of FKBP5 intron 7 methylation in relation to PTSD symptom trajectories post-rape.