Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Department of Regenerative Medicine, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
PLoS One. 2020 Sep 29;15(9):e0239196. doi: 10.1371/journal.pone.0239196. eCollection 2020.
The aim of the present study was to (1) investigate the relationship between late-onset Alzheimer's disease (AD) and DNA methylation levels in six of the top seven AD-associated genes identified through a meta-analysis of recent genome wide association studies, APOE, BIN1, PICALM, CR1, CLU, and ABCA7, in blood, and (2) examine its applicability to the diagnosis of AD. We examined methylation differences at CpG island shores in the six genes using Sanger sequencing, and one of two groups of 48 AD patients and 48 elderly controls was used for a test or replication analysis. We found that methylation levels in three out of the six genes, CR1, CLU, and PICALM, were significantly lower in AD subjects. The combination of CLU methylation levels and the APOE genotype classified AD patients with AUC = 0.84 and 0.80 in the test and replication analyses, respectively. Our study implicates methylation differences at the CpG island shores of AD-associated genes in the onset of AD and suggests their diagnostic value.
(1) 通过对最近全基因组关联研究的荟萃分析确定的前 7 个 AD 相关基因（APOE、BIN1、PICALM、CR1、CLU、和 ABCA7）中的 6 个基因（APOE、BIN1、PICALM、CR1、CLU、和 ABCA7）在血液中的 DNA 甲基化水平与迟发性阿尔茨海默病（AD）之间的关系进行研究；(2) 检验其在 AD 诊断中的适用性。我们使用 Sanger 测序检测了这 6 个基因的 CpG 岛侧翼的甲基化差异，并用两组 48 名 AD 患者和 48 名老年对照进行了测试或复制分析。我们发现，在 AD 患者中，有 3 个基因（CR1、CLU 和 PICALM）的甲基化水平显著降低。CLU 甲基化水平与 APOE 基因型的组合在测试和复制分析中分别将 AD 患者的 AUC 分类为 0.84 和 0.80。我们的研究提示 AD 相关基因的 CpG 岛侧翼甲基化差异与 AD 的发病机制有关，并提示其具有诊断价值。
