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先天免疫、神经内分泌和核因子-κB(NF-κB)系统的基因表达改变与军人创伤后应激障碍有关。

Altered gene expression of the innate immune, neuroendocrine, and nuclear factor-kappa B (NF-κB) systems is associated with posttraumatic stress disorder in military personnel.

机构信息

National Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.

National Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA; Henry M Jackson Foundation for The Advancement of Military Medicine, 6720A Rockledge Drive #100, Bethesda, MD 20817, USA.

出版信息

J Anxiety Disord. 2016 Mar;38:9-20. doi: 10.1016/j.janxdis.2015.12.004. Epub 2015 Dec 10.

Abstract

Whole transcriptome analysis provides an unbiased examination of biological activity, and likely, unique insight into the mechanisms underlying posttraumatic stress disorder (PTSD) and comorbid depression and traumatic brain injury. This study compared gene-expression profiles in military personnel with PTSD (n=28) and matched controls without PTSD (n=27) using HG-U133 Plus 2.0 microarrays (Affymetrix), which contain 54,675 probe sets representing more than 38,500 genes. Analysis of expression profiles revealed 203 differentially expressed genes in PTSD, of which 72% were upregulated. Using Partek Genomics Suite 6.6, differentially expressed transcription clusters were filtered based on a selection criterion of ≥1.5 relative fold change at a false discovery rate of ≤5%. Ingenuity Pathway Analysis (Qiagen) of the differentially expressed genes indicated a dysregulation of genes associated with the innate immune, neuroendocrine, and NF-κB systems. These findings provide novel insights that may lead to new pharmaceutical agents for PTSD treatments and help mitigate mental and physical comorbidity risk.

摘要

全转录组分析提供了对生物活性的无偏检验,并且可能为创伤后应激障碍(PTSD)和并发抑郁及创伤性脑损伤的潜在机制提供独特的见解。本研究使用 HG-U133 Plus 2.0 微阵列(Affymetrix)比较了 PTSD 患者(n=28)和无 PTSD 匹配对照组(n=27)的基因表达谱,该微阵列包含代表超过 38500 个基因的 54675 个探针集。表达谱分析显示 PTSD 中有 203 个差异表达基因,其中 72%上调。使用 Partek Genomics Suite 6.6,基于假发现率≤5%和相对倍数变化≥1.5 的选择标准,对差异表达转录簇进行过滤。差异表达基因的 Ingenuity 通路分析(Qiagen)表明与先天免疫、神经内分泌和 NF-κB 系统相关的基因失调。这些发现提供了新的见解,可能为 PTSD 治疗带来新的药物,并有助于减轻精神和身体共病风险。

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