Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation

患有创伤后应激障碍的退伍军人的免疫系统网络失调是 miRNA 表达和 DNA 甲基化改变的结果

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作者:Marpe Bam, Xiaoming Yang, Elizabeth E Zumbrun, Yin Zhong, Juhua Zhou, Jay P Ginsberg, Quinne Leyden, Jiajia Zhang, Prakash S Nagarkatti, Mitzi Nagarkatti

Abstract

Post-traumatic stress disorder patients experience chronic systemic inflammation. However, the molecular pathways involved and mechanisms regulating the expression of genes involved in inflammatory pathways in PTSD are reported inadequately. Through RNA sequencing and miRNA microarray, we identified 326 genes and 190 miRNAs that were significantly different in their expression levels in the PBMCs of PTSD patients. Expression pairing of the differentially expressed genes and miRNAs indicated an inverse relationship in their expression. Functional analysis of the differentially expressed genes indicated their involvement in the canonical pathways specific to immune system biology. DNA methylation analysis of differentially expressed genes also showed a gradual trend towards differences between control and PTSD patients, again indicating a possible role of this epigenetic mechanism in PTSD inflammation. Overall, combining data from the three techniques provided a holistic view of several pathways in which the differentially expressed genes were impacted through epigenetic mechanisms, in PTSD. Thus, analysis combining data from RNA-Seq, miRNA array and DNA methylation, can provide key evidence about dysregulated pathways and the controlling mechanism in PTSD. Most importantly, the present study provides further evidence that inflammation in PTSD could be epigenetically regulated.

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