Injuries/Violence
Blast Traumatic Brain Injury and Long-Term DNA Methylation in Select Immune Gene Promoter Regions and Repetitive Elements: A Repeated Measures Case-Control Study Among U.S. Military Service Members Jordan McAdam* Jordan McAdam Jennifer Rusiecki Ann Meyer Zygmunt Galdzicki Celia Byrne Louis French
Background: Blast traumatic brain injury (bTBI) is a major source of morbidity and mortality, including neurological deterioration, among military service members (MSM) deployed to conflict regions. Evidence suggests that TBI may induce an immune response, however few studies evaluated DNA methylation (DNAm) patterns of immune-related genes associated with TBI. We evaluated differences in DNA methylation (DNAm) at various loci on inflammatory response genes measured in uniquely available pre- and post-deployment serum samples from U.S. MSM with and without bTBI.
Methods: We obtained samples from the Department of Defense Serum Repository from 150 bTBI cases (93 mild; 57 moderate/severe) and 50 controls, frequency matched by age, sex (male, female), and race (White, Black, Other). Both cases and controls were <40 years of age at their first deployment to Afghanistan or Iraq. DNAm was quantified via Pyrosequencing for nine inflammatory response genes and two markers of global methylation. We conducted multivariate ANOVA to compare the adjusted mean differences in DNAm from pre- to post-deployment between cases and controls at each locus.
Results: The mean (standard deviation) time between cases’ diagnosis and their post-deployment serum was 315.8 (261.1) days. For IL8 gene (CXCL8) loci, the statistically significant differences in DNAm from pre to post-deployment samples were larger among controls than for moderate/severe cases (p<0.05). In contrast, for one IL10 gene locus, the statistically significant difference in DNAm from pre to post-deployment samples was larger among moderate/severe cases than controls. No other clear or consistent trends in DNAm were noted for loci of other genes.
Conclusions: These findings suggest differences in DNAm at some loci of IL8 and Il10 genes may be associated with bTBI injury. These results need to be evaluated in other studies that are able to account for treatment and blast exposure training.
Disclaimer: The opinions and assertions expressed herein do not reflect the official policy or position of the Uniformed Services University of the Health Sciences, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., or the Department of Defense.