Epigenetic Patterns of TBI: DNA Methylation in Serum of OIF/OEF Service Members
HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
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The purpose of our investigation is to elucidate how patterns of DNA methylation may vary by TBI diagnosis and by severity of the disease. TBI cases with existing serum samples housed at the Department of Defense Serum Repository DoDSR will be identified by searching the clinical database of TBI patients at Walter Reed Army Medical Center WRAMC for those cases who were diagnosed with a non-penetrating blast TBI mild, moderate, severe, from February of 2003 to present. Personnel at the DoDSR will then search the DMSS database for those members with at least one serum sample taken before their first deployment and one serum sample taken after their first deployment. We will identify an appropriate control group, frequency matched on various demographics of cases. For each TBI case and control, a serum sample drawn prior to and post first OIFOEF deployment will be identified. DNA will be extracted from each serum sample, and percent methylated cytosine mC quantified in the promoter regions of the following cytokines IL-1 , IL-6, IL-8, IL-10, and cyclin A1 and D3 and in a global nucleotide element. Comparisons will be made between cases stratified into mild, moderate, and severe and controls and between pre- and post-deployments for both cases and controls. We will also look at the levels of cytokines in residual serum not needed for DNA extraction. Since the start of thi study we have been going through the WRAMC IRB process, which has been lengthy, in order to carry out the linkage of case IDs between WRAMC and DoDSR. We have applied for a no-cost extension on the study. This study will help to elucidate the molecular sequelae of brain injury and will fuel novel therapeutic approaches to TBI therapy, particularly since modifications in DNA methylation can potentially be reversed.
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