Gene Expression and Methylation Signatures ofMAN2C1are Associated with PTSD

Abstract

Abstract. As potential regulators of DNA accessibility and activity, epigenetic modifications offer a mechanism by which the environment can moderate the effects of genes. To date, however, there have been relatively few studies assessing epigenetic modifications associated with post-traumatic stress disorder (PTSD). Here we investigate PTSD-associated methylation differences in 33 genes previously shown to differ in whole blood-derived gene expression levels between those with vs. without the disorder. Drawing on DNA samples similarly obtained from whole blood in 100 individuals, 23 with and 77 without lifetime PTSD, we used methylation microarray data to assess whether these 33 candidate genes showed epigenetic signatures indicative of increased risk for, or resilience to, PTSD. Logistic regression analyses were performed to assess the main and interacting effects of candidate genes' methylation values and number of potentially traumatic events (PTEs), adjusting for age and other covariates. Results revealed that only one candidate gene -MAN2C1 -showed a significant methylation x PTE interaction, such that those with both higher MAN2C1 methylation and greater exposure to PTEs showed a marked increase in risk of lifetime PTSD (OR 4.35, 95% CI: 1.07, 17.77, p = 0.04). These results indicate that MAN2C1 methylation levels modify cumulative traumatic burden on risk of PTSD, and suggest that both gene expression and epigenetic changes at specific loci are associated with this disorder.

Dual Functions for Cytosolic α-Mannosidase (Man2C1)

“…In one investigation, transgene expression of Man2C1 promoted tumor progress in mice (18); later it was found that Man2C1 overexpression could attenuate PTEN function in prostate cancer cells (20). Con- relative to control subjects (43). None of these reports, however, successfully tied these phenotypic consequences with the Man2C1 enzymatic activity.…”

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

“…The changes in inflammatory gene expression that have been described in individuals with PTSD are coincident with alterations in epigenetic markers, as immune-related methylation profiles are altered in PTSD (Heinzelmann and Gill, 2013). Methylation of mannosidase, alpha class 2C, member 1 (MAN2C1), acid phosphatase 5 (ACP5), and tolllike receptor (TLR) 8, which are genes involved in immune function, was found to be altered in PTSD Uddin et al, 2011). Decreased methylation of immune-related genes TLR1 and TLR3 has also been described in individuals with PTSD in a manner related to the severity and burden of the traumatic event (Uddin et al, 2010).…”

The urban environment and mental disorders

“…[35][36][37] when accounting for individual income or exposure to stressful or adverse circumstances. 6,9,10 Living in neighborhoods characterized by residential racial segregation is associated with a greater risk of depression and anxiety, compared to living in less segregated neighborhoods.…”