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Mult Scler. 2018 Sep;24(10):1288-1300. doi: 10.1177/1352458517721356. Epub 2017 Aug 2.

Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes.

Author information

1
Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
2
Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Department of Genetics, Medical School of Ribeirão Preto, São Paulo University, Ribeirão Preto, Brazil.
3
Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Science for Life Laboratory, Stockholm, Sweden.
4
Cardiovascular Epidemiology and Genetics Group, Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, Spain/ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
5
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
6
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
7
College of Public Health, University of Kentucky, Lexington, KY, USA.
8
Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Science for Life Laboratory, Stockholm, Sweden/ Biological and Environmental Sciences and Engineering Division, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
9
Unit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Mucosal & Salivary Biology Division, Dental Institute, King's College London, London, UK.

Abstract

BACKGROUND:

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.

OBJECTIVE:

We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).

METHODS:

We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.

RESULTS:

We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes.

CONCLUSION:

Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.

KEYWORDS:

CD4+ T cells; DNA methylation; autoimmunity; epigenetics; miR-21; microRNAs; multiple sclerosis; relapsing-remitting

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