CpG Methylation in the 1F Promoter of the NR3C1 Gene and its Biomarker Potential in Post-Traumatic Stress Disorder

Abstract

PTSD is a disorder that is described to cause by disruption of psychoneurological and biological processes in military personnel due to war-related trauma, excessive stress and exposure to extreme environments. Specifically, stability of the means of stress response is also influenced by epigenetic regulation of the glucocorticoid receptor gene (NR3C1). In this research, “in silico” methods of CpG methylation at a level and location in the 1F promoter region of NR3C1 gene was conducted. We examined exon 1F promoter of the glucocorticoid receptor gene (NR3C1) of peripheral blood of group of individuals aged 20-24 (46 XY males, 46 XX females). The degree of CpG methylation was higher in females (β ≈ 0.8-1.0) compared with males (β ≈ 0.5-0.7), showing that there was a high sensitivity to methylation and a high epigenetic activity at the locus. Variability observed indicates that the 1F promoter is a major site of the individual difference in stress responsivity. Due to the potential to alter the NR3C1 expression with the help of methylation of this region, such patterns can affect cortisol regulation and the functioning of the HPA-axis, which could possibly support the maintenance of stress responses following military trauma and predisposes to PTSD. On the whole, the presented analyses show that CpG methylation in the 1F promoter of the NR3C1 gene could be one of the molecular predictors of stress tolerance and adaptation to psychological stress in a military environment. This region could be assessed as an early diagnostic and prognostic epigenetic biomarker of PTSD.