National Research Council of Canada, Digital Technologies Research Centre, Ottawa, Canada.
Oakland University-William Beaumont School of Medicine, Rochester, MI, 48309, USA.
Commun Biol. 2022 Nov 22;5(1):1279. doi: 10.1038/s42003-022-03965-x.
Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measure genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compare them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identify 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions. Genes associated with the DMCs are linked to "Parkinson's disease" and "metabolic pathway", as well as the diseases of "severe intellectual disability" and "mood disorders". Overall, our study highlights previously unreported DMCs offering insights into DLB pathogenesis with the possibility that some of these could be used as biomarkers of DLB in the future.
路易体痴呆症(DLB)是一种常见的痴呆症,其发病与已知的遗传和环境相互作用有关。然而,反映这些基因-环境相互作用的潜在表观遗传机制研究甚少。在此,我们使用 Illumina MethylationEPIC 芯片,测量了 15 例经病理证实的 DLB 脑和 16 例认知正常对照的死后脑组织(布罗德曼 7 区)的全基因组 DNA 甲基化谱。我们在两组之间鉴定出 17 个差异甲基化 CpG(DMC)和 17 个差异甲基化区域(DMR)。DMC 主要位于 CpG 岛、启动子和第一外显子区。与 DMC 相关的基因与“帕金森病”和“代谢途径”以及“严重智力障碍”和“情绪障碍”等疾病相关。总的来说,我们的研究强调了以前未报道的 DMC,为 DLB 的发病机制提供了新的见解,未来这些 DMC 中的一些可能被用作 DLB 的生物标志物。