从三个独立队列中证明的神经营养基因 DNA 甲基化与年龄的关系：谵妄状态的差异。
The relationship between DNA methylation in neurotrophic genes and age as evidenced from three independent cohorts: differences by delirium status.
机构信息
Department of Psychiatry, University of Iowa, Iowa City, IA, USA; Department of Psychiatry, School of Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
Neurobiol Aging. 2020 Oct;94:227-235. doi: 10.1016/j.neurobiolaging.2020.06.003. Epub 2020 Jun 12.
We previously reported the association between DNA methylation (DNAm) of pro-inflammatory cytokine genes and age. In addition, neurotrophic factors are known to be associated with age and neurocognitive disorders. Therefore, we hypothesized that DNAm of neurotrophic genes change with age, especially in delirium patients. DNAm was analyzed using the Illumina HumanMethylation450 or HumanMethylationEPIC BeadChip Kit in 3 independent cohorts: blood from 383 Grady Trauma Project subjects, brain from 21 neurosurgery patients, and blood from 87 inpatients with and without delirium. Both blood and brain samples showed that most of the DNAm of neurotrophic genes were positively correlated with age. Furthermore, DNAm of neurotrophic genes was more positively correlated with age in delirium cases than in non-delirium controls. These findings support our hypothesis that the neurotrophic genes may be epigenetically modulated with age, and this process may be contributing to the pathophysiology of delirium.
我们之前报道了促炎细胞因子基因的 DNA 甲基化 (DNAm) 与年龄之间的关联。此外，神经营养因子与年龄和神经认知障碍有关。因此，我们假设神经营养基因的 DNAm 会随着年龄的增长而发生变化，尤其是在谵妄患者中。在 3 个独立的队列中使用 Illumina HumanMethylation450 或 HumanMethylationEPIC BeadChip Kit 分析 DNAm：383 名 Grady 创伤项目受试者的血液、21 名神经外科患者的大脑和 87 名伴有或不伴有谵妄的住院患者的血液。血液和大脑样本均显示，大多数神经营养基因的 DNAm 与年龄呈正相关。此外，与非谵妄对照组相比，谵妄病例中神经营养基因的 DNAm 与年龄的相关性更强。这些发现支持我们的假设，即神经营养基因可能会随着年龄的增长而发生表观遗传调节，这一过程可能有助于谵妄的病理生理学。
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