Kiselev I S, Kulakova O G, Baturina O A, Kabilov M R, Boyko A N, Favorova O O
Pirogov Russian National Research Medical University, Moscow, Russia.
Institute of Chemical Biology and Fundamental Medicine - Genomics Core Facility, Novosibirsk, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(7. Vyp. 2):60-64. doi: 10.17116/jnevro202312307260.
To study the whole-genome DNA methylation profiles of peripheral blood mononuclear blood cells (PBMCs) of patients with relapsing-remitting multiple sclerosis (RRMS) in remission and relapse in order to assess the contribution of this epigenetic mechanism of gene expression regulation to the activity of the pathological process.
Eight patients with RRMS in remission and 6 patients in relapse were included in the study. Methylation levels of DNA CpG sites in PBMCs were analyzed using Infinium HumanMethylation450 BeadChip DNA microarrays.
Seven differentially methylated positions (DMPs) were identified, of which 3 were hypermethylated (cg02981003, cg18486102, cg19533582) and 4 were hypomethylated (cg16814680, cg1964802, cg18584440, cg08291996) during RRMS relapse. Five DMPs are located in protein-coding genes (, , , , ), one in microRNA gene (), and one in an intergenic region. For all identified DMPs, we observed a change in DNA methylation levels of more than 20% (range 20.2-57.5%). Hierarchical clustering of DNA samples on the heatmap shows their clear aggregation into separate clusters corresponding to RRMS patients in the stages of relapse and remission.
For the first time it was shown that during relapse and remission of RRMS there are differences in the DNA methylation profile that allow discrimination between these clinical stages. These data indicate the involvement of the epigenetic mechanism of DNA methylation in the activation of the pathological process in RRMS.
研究复发缓解型多发性硬化症（RRMS）患者缓解期和复发期外周血单个核细胞（PBMC）的全基因组DNA甲基化谱，以评估这种基因表达调控的表观遗传机制对病理过程活动的作用。
本研究纳入8例RRMS缓解期患者和6例复发期患者。使用Infinium HumanMethylation450 BeadChip DNA微阵列分析PBMC中DNA CpG位点的甲基化水平。
共鉴定出7个差异甲基化位点（DMP），其中3个在RRMS复发期间发生高甲基化（cg02981003、cg18486102、cg19533582），4个发生低甲基化（cg16814680、cg1964802、cg18584440、cg08291996）。5个DMP位于蛋白质编码基因中（，，，，），1个位于微小RNA基因中（），1个位于基因间区域。对于所有鉴定出的DMP，我们观察到DNA甲基化水平变化超过20%（范围为20.2 - 57.5%）。热图上DNA样本的层次聚类显示它们明显聚为对应RRMS患者复发期和缓解期的单独簇。
首次表明在RRMS复发和缓解期间，DNA甲基化谱存在差异，可区分这些临床阶段。这些数据表明DNA甲基化的表观遗传机制参与了RRMS病理过程的激活。
