DNA methylation may mediate persistent changes in gene function following 
chronic stress. To examine this hypothesis, we evaluated African American 
subjects matched by age and sex, and stratified into four groups by 
post-traumatic stress disorder (PTSD) diagnosis and history of child abuse. 
Total Life Stress (TLS) was also assessed in all subjects. We evaluated DNA 
extracted from peripheral blood using the HumanMethylation27 BeadChip and 
analyzed both global and site-specific methylation. Methylation levels were 
examined for association with PTSD, child abuse history, and TLS using a linear 
mixed model adjusted for age, sex, and chip effects. Global methylation was 
increased in subjects with PTSD. CpG sites in five genes (TPR, CLEC9A, APC5, 
ANXA2, and TLR8) were differentially methylated in subjects with PTSD. 
Additionally, a CpG site in NPFFR2 was associated with TLS after adjustment for 
multiple testing. Notably, many of these genes have been previously associated 
with inflammation. Given these results and reports of immune dysregulation 
associated with trauma history, we compared plasma cytokine levels in these 
subjects and found IL4, IL2, and TNFα levels associated with PTSD, child abuse, 
and TLS. Together, these results suggest that psychosocial stress may alter 
global and gene-specific DNA methylation patterns potentially associated with 
peripheral immune dysregulation. Our results suggest the need for further 
research on the role of DNA methylation in stress-related illnesses.