Full text 2025

Epigenetics in persons living with HIV: trauma, coping, and <i>FKBP5</i> and <i>SLC6A4</i> methylation

Tomlinson CJ, Ryniker L, Cook HM, et al.

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Abstract

<h4>Aim</h4>People living with HIV (PLWH) have an increased risk for lifetime trauma and mental health difficulties. However, no studies have evaluated stress-related genes in relation to early-life adversity, lifetime trauma, or post-traumatic stress disorder (PTSD) in PLWH.<h4>Methods</h4>Using bisulfite pyrosequencing, we evaluated DNA methylation (DNAm) in intron 7 of FKBP5, a glucocorticoid feedback regulator, and in the promoter of SLC6A4, the serotonin transporter gene, in whole blood of a random sample of 70 PLWH recruited from an HIV program, and 51 individuals 2 years later (<i>n</i> = 48 at both time points). Exploratory regression analyses were conducted with DNAm in relation to trauma exposure, mental health symptoms, and coping strategies.<h4>Results</h4>Higher DNAm at one site of SLC6A4 was associated with lower levels of anxiety (B = -0.62 (SE = 0.23), <i>p</i> = 0.0109), depression (B = -0.06 (SE = 0.03), <i>p</i> = 0.0435), and PTSD symptoms at baseline (B = -0.03 (SE = 0.01), <i>p</i> = 0.0374). DNAm at FKBP5 was negatively associated with measures of anxiety (B = -0.30 (SE = 0.07), <i>p</i> = 0.0001) and depression symptoms (B = -0.2 (SE = 0.10), <i>p</i> = 0.0103). Various coping strategies were also associated with sites in both genes across time points, e.g. self-blame and substance use.<h4>Conclusion</h4>Our findings generate intriguing hypotheses linking mental health symptoms and DNA methylation, to be replicated with larger samples.

Keywords

Depression Anxiety SLC6A4 Ptsd People Living With Hiv Fkbp5 Stress-related Genes Lifetime Trauma