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Hypermethylation of <i>MIR21</i> 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

Sabrina RuhrmannDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, SwedenEwoud EwingDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, SwedenEliane PiketDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, SwedenLara KularDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, SwedenJulio C. C. LorenziDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Department of Genetics, Medical School of Ribeirão Preto, São Paulo University, Ribeirão Preto, BrazilSunjay Jude FernandesUnit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Science for Life Laboratory, Stockholm, SwedenHiromasa MorikawaUnit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Science for Life Laboratory, Stockholm, SwedenShahin AeinehbandDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, SwedenSergi Sayols-BaixerasCardiovascular Epidemiology and Genetics Group, Institut Hospital del Mar d’Investigacions Mediques (IMIM), Barcelona, Spain/ Universitat Pompeu Fabra (UPF), Barcelona, SpainStella AslibekyanDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USADevin AbsherHudsonAlpha Institute for Biotechnology, Huntsville, AL, USADonna K. ArnettCollege of Public Health, University of Kentucky, Lexington, KY, USAJesper TegnérKarolinska InstitutetDavid Gómez-CabreroUnit 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, UKFredrik PiehlDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, SwedenMaja JagodicDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

2017en

ABI

Annotatsiya

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.

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DOI: 10.1177/1352458517721356

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