Epigenetic Regulation of Glucocorticoid Receptor Sensitivity and Immune Function in Adults Exposed to Early Childhood Adversity in Northern Nigeria

Early childhood adversity programmes the hypothalamic-pituitary-adrenal axis through epigenetic modifications to glucocorticoid receptor gene expression, with lasting consequences for immune physiology, yet these mechanisms have not been investigated in African populations facing unique adversity profiles. This study investigated glucocorticoid receptor gene methylation, receptor sensitivity, and immune function in adults reporting early childhood adversity in Kano State, North West Nigeria. A case-control design recruited 80 adults with documented early childhood adversity by validated retrospective questionnaire and 80 controls. NR3C1 glucocorticoid receptor gene promoter methylation was quantified from peripheral blood leukocytes by bisulphite pyrosequencing. Glucocorticoid sensitivity was assessed by ex vivo dexamethasone suppression of lipopolysaccharide-stimulated cytokine production. Immune phenotyping characterised T-regulatory cell and natural killer cell populations. Salivary cortisol diurnal profiles were obtained. Path analysis and ANCOVA were applied. Results demonstrated significantly elevated NR3C1 methylation in adversity-exposed adults, which predicted glucocorticoid resistance in ex vivo testing. Glucocorticoid-resistant participants had significantly reduced T-regulatory cell frequencies and elevated pro-inflammatory cytokine release. Flattened diurnal cortisol was also associated with higher methylation. This study provides the first epigenetic physiological evidence linking early life stress to adult immune dysregulation in a Nigerian population, making a theoretically original contribution. Trauma-sensitive health policy and epigenetic literacy in clinical practice are advocated. Keywords: epigenetics, glucocorticoid receptor, early adversity, immune function, northern Nigeria.