Methylation of the AIM2 gene: An epigenetic mediator of PTSD-related inflammation and neuropathology plasma biomarkers.
Methylation of the AIM2 gene: An epigenetic mediator of PTSD-related inflammation and neuropathology plasma biomarkers.
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DOI：
10.1002/da.23247
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发表时间：
2022-04
影响因子：
7.4
通讯作者：
Miller MW
中科院分区：
文献类型：
--
作者：
Hawn SE;Neale Z;Wolf EJ;Zhao X;Pierce M;Fein-Schaffer D;Milberg W;McGlinchey R;Logue M;Miller MW
创伤后应激障碍 (PTSD) 与炎症和各种形式的慢性疾病有关。黑色素瘤 2 缺失 (AIM2) 基因与炎症和焦虑机制有关，该基因 (cg10636246) 特定位点的甲基化先前已被证明会影响 PTSD 与血液中 C 反应蛋白水平升高之间的关联。我们在一组 9/11 后美国退伍军人中测试了这种关联是否可以扩展到其他炎症指标和基于血浆的神经病理学测量。使用贝叶斯方法，对中介模型进行了横向（n = 478）和纵向（n = 298）测试。使用超灵敏单分子阵列 (Simoa®) 技术测量炎症和神经病理学的外周标志物。分析揭示了 PTSD 症状严重程度对炎症（白细胞介素 [IL]6、IL-10、肿瘤坏死因子-α）外周指数的间接影响；间接标准化 [std.] ß 范围 = 0.018–0.023，所有 p 值均针对多重测试进行调整 [padj] < 0.05）和神经病理学（神经丝光） [美国橄榄球联盟]；间接标准。 ß =−0.018, padj = 0.02) 通过 AIM2 甲基化。在控制基线 IL-10 的后续评估中预测 IL-10 时（间接 std.ß = -0.018，padj = 0.04），这种间接效应也很明显。鉴于 AIM2 甲基化介导 PTSD 症状与多种炎症和神经病理学标志物之间的关联，我们的结果表明，AIM2 甲基化可能为索引与这些炎症和神经病理学外周指标相关的不良健康结果风险提供临床实用性。结果还表明，炎症和神经病理学频繁同时发生可能存在共同的病因。
Posttraumatic stress disorder (PTSD) is associated with inflammation and various forms of chronic disease. The Absent in Melanoma 2 (AIM2) gene has been implicated in mechanisms of inflammation and anxiety, and methylation at a particular locus in this gene (cg10636246) has previously been shown to influence the association between PTSD and elevated C-reactive protein levels in blood. We tested if this association might extend to other indicators of inflammation and to plasma-based measures of neuropathology in a cohort of post-9/11 US military veterans. Using a Bayesian approach, mediation models were tested cross-sectionally (n = 478) and longitudinally (n = 298). Peripheral markers of inflammation and neuropathology were measured with ultra-sensitive Single Molecule Array (Simoa®) technology. Analyses revealed indirect effects of PTSD symptom severity on peripheral indices of both inflammation (interleukin [IL]6, IL-10, tumor necrosis factor-α; indirect standardized [std.] ß range = 0.018–0.023, all p-values adjusted for multiple testing [padj] < 0.05) and neuropathology (neurofilament light [NFL]; indirect std. ß =−0.018, padj = 0.02) via AIM2 methylation. This indirect effect was also evident when predicting IL-10 at a follow-up assessment (indirect std. ß = −0.018, padj = 0.04) controlling for baseline IL-10. Given that AIM2 methylation mediated the association between PTSD symptoms and multiple inflammatory and neuropathology markers, our results suggest that AIM2 methylation may offer clinical utility for indexing risk for adverse health outcomes associated with these peripheral indices of inflammation and neuropathology. Results also suggest a possible shared etiology underlying the frequent co-occurrence of inflammation and neuropathology.
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