Epigenetics of neuroinflammation: Immune response, inflammatory response and cholinergic synaptic involvement evidenced by genome-wide DNA methylation analysis of delirious inpatients.

Autor: Saito T; Department of Psychiatry, University of Iowa, Iowa City, IA, USA; Department of Psychiatry, School of Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan., Toda H; Department of Psychiatry, School of Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan., Duncan GN; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Jellison SS; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Yu T; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Klisares MJ; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Daniel S; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Andreasen AJ; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Leyden LR; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Hellman MM; Department of Psychiatry, University of Iowa, Iowa City, IA, USA., Shinozaki E; Department of Internal Medicine, University of Iowa, Iowa City, IA, USA., Lee S; Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA., Yoshino A; Department of Psychiatry, School of Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan., Cho HR; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA., Shinozaki G; Department of Psychiatry, University of Iowa, Iowa City, IA, USA; Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA, USA. Electronic address: gen-shinozaki@uiowa.edu.
Jazyk: angličtina
Zdroj: Journal of psychiatric research [J Psychiatr Res] 2020 Oct; Vol. 129, pp. 61-65. Date of Electronic Publication: 2020 Jun 06.
DOI: 10.1016/j.jpsychires.2020.06.005
Abstrakt: Previously our study has shown that the DNA methylation (DNAm) levels at CpG sites in the pro-inflammatory cytokine gene, TNF-alpha, decrease along with aging, suggesting the potential role of DNAm in aging and heightened inflammatory process leading to increased risk for delirium. However, DNAm differences between delirium cases and non-delirium controls have not been investigated directly. Therefore, we examined genome-wide DNAm differences in blood between patients with delirium and controls to identify useful epigenetic biomarkers for delirium. Data from a total of 87 subjects (43 delirium cases) were analyzed by a genome-wide DNAm case-control association study. A genome-wide significant CpG site near the gene of LDLRAD4 was identified (p = 5.07E-8). In addition, over-representation analysis showed several significant pathways with a false discovery rate adjusted p-value < 0.05. The top pathway with a Gene Ontology term was immune response, and the second top pathway with a Kyoto Encyclopedia of Genes and Genomes term was cholinergic synapse. Significant DNAm differences related to immune/inflammatory response were shown both at gene and pathway levels between patients with delirium and non-delirium controls. This finding indicates that DNAm status in blood has the potential to be used as epigenetic biomarkers for delirium.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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