2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 57(2023) N 5 p. 836-842; DOI 10.1134/S0026893323050047 Full Text

I.S. Kiselev1*, O.G. Kulakova1, O.A. Baturina2, M.R. Kabilov2, A.N. Boyko1,3, O.O. Favorova1

DNA Methylation Profile of CD14+ Monocytes Changes in Primary Progressive Multiple Sclerosis

1Pirogov Russian National Research Medical University, Moscow, 117997 Russia
2Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia
3Federal Center for Brain and Neurotechnology, Federal Medical-Biological Agency, Moscow, 117997 Russia

Received - 2023-04-27; Revised - 2023-04-27; Accepted - 2023-05-02

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.

primary progressive multiple sclerosis, inflammation, neurodegeneration, DNA methylation, epigenetic regulation