National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System, Boston, MA, USA.
Brain Behav Immun. 2018 Jan;67:194-202. doi: 10.1016/j.bbi.2017.08.022. Epub 2017 Sep 1.
Recent studies have implicated inflammatory processes in the pathophysiology of posttraumatic stress disorder (PTSD). C-reactive protein (CRP) is a widely-used measure of peripheral inflammation, but little is known about the genetic and epigenetic factors that influence blood levels of C-reactive protein (CRP) in individuals with PTSD.
Participants were 286 U.S. military veterans of post-9/11 conflicts (57% with current PTSD). Analyses focused on single nucleotide polymorphisms (SNPs) in the CRP gene and DNA methylation at cg10636246 in AIM2-a locus recently linked to CRP levels through results from a large-scale epigenome-wide association study.
PTSD was positively correlated with serum CRP levels with PTSD cases more likely to have CRP levels in the clinically-elevated range compared to those without a PTSD diagnosis. Multivariate analyses that controlled for white blood cell proportions, genetic principal components, age and sex, showed this association to be mediated by methylation at the AIM2 locus. rs3091244, a functional SNP in the CRP promoter region, moderated the association between lifetime trauma exposure and current PTSD severity. Analyses also revealed that the top SNPs from the largest genome-wide association study of CRP conducted to date (rs1205 and rs2794520) significantly interacted with PTSD to influence CRP levels.
These findings provide new insights into genetic and epigenetic mechanisms of inflammatory processes in the pathophysiology of PTSD and point to new directions for biomarker identification and treatment development for patients with PTSD.
最近的研究表明，创伤后应激障碍（PTSD）的病理生理学涉及炎症过程。C 反应蛋白（CRP）是一种广泛使用的外周炎症测量指标，但对于影响 PTSD 个体 CRP 血液水平的遗传和表观遗传因素知之甚少。
参与者是 286 名美国 9/11 后冲突的退伍军人（57%有当前的 PTSD）。分析集中在 CRP 基因中的单核苷酸多态性（SNP）和 AIM2 基因座中的 cg10636246 处的 DNA 甲基化，该基因座最近通过大规模全基因组关联研究的结果与 CRP 水平相关联。
PTSD 与血清 CRP 水平呈正相关，与没有 PTSD 诊断的人相比，PTSD 病例更有可能处于临床升高范围的 CRP 水平。多变量分析控制了白细胞比例、遗传主成分、年龄和性别，表明这种关联是由 AIM2 基因座的甲基化介导的。CRP 启动子区域的功能性 SNP rs3091244 调节了终生创伤暴露与当前 PTSD 严重程度之间的关联。分析还表明，迄今为止进行的最大 CRP 全基因组关联研究的顶级 SNP（rs1205 和 rs2794520）与 PTSD 显著相互作用，影响 CRP 水平。
这些发现为 PTSD 病理生理学中炎症过程的遗传和表观遗传机制提供了新的见解，并为 PTSD 患者的生物标志物识别和治疗发展指明了新的方向。
