LAUSR

&NA; Mild traumatic brain injury (mTBI) occurred in 15–30% of Veterans returning from Iraq and Afghanistan. We examined whether DNA methylation of the apolipoprotein E (APOE) gene promoter region or plasma ApoE protein levels are altered in mTBI. APOE promoter region DNA methylation, APOE genotype, and plasma ApoE concentration were determined in 87 Veterans with or without mTBI who were recruited from 2010‐2014. Plasma ApoE concentration was found to be associated with Posttraumatic Stress Disorder (PTSD) symptom severity ratings by hierarchical linear regression (p = .013) and ANCOVA (p = .007). Hierarchical linear regression revealed that plasma ApoE concentration was associated with APOE‐&egr;4 genotype status (p=.022). Higher ApoE plasma levels were found in &egr;3/&egr;3 Veterans than in APOE‐&egr;4 carriers (p = .031). Furthermore, plasma ApoE concentration was associated experiment‐wise with DNA methylation at CpG sites ‐877 (p = .021), and ‐775 (p = .014). The interaction between APOE‐&egr;4 genotype and having a PTSD diagnosis was associated with DNA methylation at CpG site ‐675 (p = .009). HighlightsPlasma ApoE was associated with PTSD and APOE‐&egr;4 genotype status.Interaction observed among APOE‐&egr;4 genotype, PTSD diagnosis, and APOE methylation.