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, 117997 Russia.
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia.
Mol Biol (Mosk). 2023 Sep-Oct;57(5):819-826.
Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system, which is characterized by significant clinical heterogeneity. Primary progressive MS (PPMS) develops in 10-15% of patients. Unlike the most common relapsing-remitting form of MS, PPMS involves steady progress of neurodegeneration and, as a consequence, a persistent gradual increase in neurological symptoms. The peculiarities of epigenetic regulation of gene expression may be one of the reasons for the differences in the pathogenesis of the two MS forms. DNA methylation is one of the key epigenetic mechanisms, which remains almost unexplored in different cell populations of PPMS patients. The goal of this work was to identify differential methylation profiles of the CpG sites in the CD14+ monocyte DNA, which characterize PPMS. A genome-wide analysis of DNA methylation in PPMS patients and healthy individuals has identified 169 differentially methylated positions (DMPs), 90.5% of which were hypermethylated in PPMS patients. More than half of all DMPs are located in/near known genes and within CpG islands and their neighboring regions, which indicates their high functional significance. We have found six differentially methylated regions (DMRs) in the OR2L13, CAT, LCLAT1, HOXA5, RNF39, and CRTAC1 genes involved in inflammation and neurodegeneration, which indicates active epigenetic regulation of their expression.
多发性硬化症（MS）是一种中枢神经系统的慢性自身免疫性炎症和神经退行性疾病，其临床异质性显著。10%-15%的患者会发展为原发性进展型多发性硬化症（PPMS）。与最常见的复发缓解型MS不同，PPMS涉及神经退行性变的稳步进展，因此神经症状持续逐渐加重。基因表达的表观遗传调控特性可能是这两种MS形式发病机制存在差异的原因之一。DNA甲基化是关键的表观遗传机制之一，在PPMS患者的不同细胞群体中几乎尚未得到研究。这项工作的目的是确定CD14+单核细胞DNA中CpG位点的差异甲基化谱，这些谱可表征PPMS。对PPMS患者和健康个体的DNA甲基化进行全基因组分析，已确定169个差异甲基化位点（DMP），其中90.5%在PPMS患者中发生高甲基化。所有DMP中超过一半位于已知基因内部/附近以及CpG岛及其邻近区域，这表明它们具有很高的功能重要性。我们在参与炎症和神经退行性变的OR2L13、CAT、LCLAT1、HOXA5、RNF39和CRTAC1基因中发现了六个差异甲基化区域（DMR），这表明它们的表达受到活跃的表观遗传调控。
