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

<b>Background:</b> 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 (<i>FKBP5</i>) is a co-chaperone and functional regulator of the glucocorticoid receptor and the HPA-axis.<b>Objective:</b> This study investigated main and interaction effects of childhood trauma and the <i>FKBP5</i> rs1360780 genotype on longitudinal <i>FKBP5</i> intron 7 methylation, and whether change in <i>FKBP5</i> methylation over time was associated with PTSD symptom severity over time.<b>Method:</b> Women who experienced rape (<i>n</i> = 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 <i>FKBP5</i> 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.<b>Results:</b> The interaction between rs1360780 genotype and childhood trauma was a significant predictor of <i>FKBP5</i> 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. <i>FKBP5</i> methylation was not a predictor of PTSD scores over time.<b>Conclusion:</b> This is the first study to investigate longitudinal change in <i>FKBP5</i> methylation in a demographically homogenous same-trauma sample. The findings implicate childhood trauma and <i>FKBP5</i> rs1360980 genotype in the trajectory of <i>FKBP5</i> methylation levels in the aftermath of rape. Further research is needed to investigate the longitudinal role of <i>FKBP5</i> intron 7 methylation in relation to PTSD symptom trajectories post-rape.