Epigenetic Patterns of PTSD: DNA Methylation In Serum of OIF/OEF Servicemembers
Final rept. 31 Mar 2008-31 Dec 2010
HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
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The molecular mechanisms involved in PTSD are not well characterized epigenetic factors could offer new insights. Gene expression studies show differences in cytokine expression signatures between PTSD patients and controls. DNA methylation is intrinsically linked to gene expression. We investigated DNA methylation patterns in repetitive DNA elements and in cytokine promoter regions in soldiers prior to OIFOEF deployment serum-derived DNA was used. PTSD cases with existing serum samples housed at the Department of Defense Serum Repository were identified via ICD-9 codes an appropriate control group was identified. For each PTSD case and control, a pre- and post-deployment serum sample was obtained. DNA was extracted and methylation quantified via pyrosequencing in the following promoter regions IGF2, EDG1, IL-8 , IL-8RA, IL- 16, IL-18, p11 and in repetitive elements LINE-1 and Alu. We made statistical comparisons via t-tests and logistic regressions for patterns of DNA methylation between cases and controls and between pre- and post-deployments of each group. The results of our study indicate that global DNA methylation as measured via Alu is a biomarker of stress incurred during deployment and potentially a marker of greater susceptibility to PTSD. The results for LINE-1 are not as clear. There were no clear patterns of cytokine promoter region hyper- or hypo-methylation. Pre-deployment, people who became PTSD cases had reduced IL-18 methylation compared to controls. Controls post-deployment had lower IGF-2 levels than they did pre-deployment. Since we used serum DNA as the biomarker and not a specific tissue derived DNA such as brain tissue, our findings could be associated with more of a response in inflammatory tissues, but not specifically in the brain. These findings should be followed up in a larger study.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research