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

Handle URI:
http://hdl.handle.net/10754/625313
Title:
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
Authors:
Ruhrmann, Sabrina; Ewing, Ewoud; Piket, Eliane; Kular, Lara; Cetrulo Lorenzi, Julio Cesar; Fernandes, Sunjay Jude; Morikawa, Hiromasa; Aeinehband, Shahin; Sayols-Baixeras, Sergi; Aslibekyan, Stella; Absher, Devin M; Arnett, Donna K; Tegner, Jesper ( 0000-0002-9568-5588 ) ; Gomez-Cabrero, David; Piehl, Fredrik; Jagodic, Maja
Abstract:
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.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).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.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.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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Ruhrmann S, Ewing E, Piket E, Kular L, Cetrulo Lorenzi JC, et al. (2017) 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. Multiple Sclerosis Journal: 135245851772135. Available: http://dx.doi.org/10.1177/1352458517721356.
Publisher:
SAGE Publications
Journal:
Multiple Sclerosis Journal
Issue Date:
2-Aug-2017
DOI:
10.1177/1352458517721356
Type:
Article
ISSN:
1352-4585; 1477-0970
Sponsors:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the Swedish Research Council, the Swedish Association for Persons with Neurological Disabilities, the Swedish Brain Foundation, Petrus and Augusta Hedlunds Foundation, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, AstraZeneca (AstraZeneca-Science for Life Laboratory collaboration) and grant R01HL104135 from the National Institutes of Health/National Heart, Lung and Blood Institute (GOLDN). S.S.-B. was funded by a contract from Instituto de Salud Carlos III FEDER (IFI14/00007) and Daniel Bravo Andreu Private Foundation. L.K. was supported by fellowship from the Margaretha af Ugglas Foundation.
Additional Links:
http://journals.sagepub.com/doi/10.1177/1352458517721356
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorRuhrmann, Sabrinaen
dc.contributor.authorEwing, Ewouden
dc.contributor.authorPiket, Elianeen
dc.contributor.authorKular, Laraen
dc.contributor.authorCetrulo Lorenzi, Julio Cesaren
dc.contributor.authorFernandes, Sunjay Judeen
dc.contributor.authorMorikawa, Hiromasaen
dc.contributor.authorAeinehband, Shahinen
dc.contributor.authorSayols-Baixeras, Sergien
dc.contributor.authorAslibekyan, Stellaen
dc.contributor.authorAbsher, Devin Men
dc.contributor.authorArnett, Donna Ken
dc.contributor.authorTegner, Jesperen
dc.contributor.authorGomez-Cabrero, Daviden
dc.contributor.authorPiehl, Fredriken
dc.contributor.authorJagodic, Majaen
dc.date.accessioned2017-08-10T11:43:33Z-
dc.date.available2017-08-10T11:43:33Z-
dc.date.issued2017-08-02en
dc.identifier.citationRuhrmann S, Ewing E, Piket E, Kular L, Cetrulo Lorenzi JC, et al. (2017) 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. Multiple Sclerosis Journal: 135245851772135. Available: http://dx.doi.org/10.1177/1352458517721356.en
dc.identifier.issn1352-4585en
dc.identifier.issn1477-0970en
dc.identifier.doi10.1177/1352458517721356en
dc.identifier.urihttp://hdl.handle.net/10754/625313-
dc.description.abstractMultiple 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.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).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.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.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.en
dc.description.sponsorshipThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the Swedish Research Council, the Swedish Association for Persons with Neurological Disabilities, the Swedish Brain Foundation, Petrus and Augusta Hedlunds Foundation, the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, AstraZeneca (AstraZeneca-Science for Life Laboratory collaboration) and grant R01HL104135 from the National Institutes of Health/National Heart, Lung and Blood Institute (GOLDN). S.S.-B. was funded by a contract from Instituto de Salud Carlos III FEDER (IFI14/00007) and Daniel Bravo Andreu Private Foundation. L.K. was supported by fellowship from the Margaretha af Ugglas Foundation.en
dc.publisherSAGE Publicationsen
dc.relation.urlhttp://journals.sagepub.com/doi/10.1177/1352458517721356en
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).en
dc.rights.urihttp://www.creativecommons.org/licenses/by/4.0/en
dc.subjectDNA methylationen
dc.subjectMultiple sclerosisen
dc.subjectAutoimmunityen
dc.subjectEpigeneticsen
dc.subjectCd4+ T Cellsen
dc.subjectMir-21en
dc.subjectRelapsing-remittingen
dc.subjectmicroRNAsen
dc.titleHypermethylation 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 genesen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalMultiple Sclerosis Journalen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.en
dc.contributor.institutionDepartment of Genetics, Medical School of Ribeirão Preto, São Paulo University, Ribeirão Preto, Brazil.en
dc.contributor.institutionScience for Life Laboratory, Stockholm, Sweden.en
dc.contributor.institutionUnit of Computational Medicine, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.en
dc.contributor.institutionUniversitat Pompeu Fabra (UPF), Barcelona, Spain.en
dc.contributor.institutionCardiovascular Epidemiology and Genetics Group, Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, Spain.en
dc.contributor.institutionDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.en
dc.contributor.institutionHudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.en
dc.contributor.institutionCollege of Public Health, University of Kentucky, Lexington, KY, USA.en
dc.contributor.institutionMucosal & Salivary Biology Division, Dental Institute, King's College London, London, UK.en
kaust.authorTegner, Jesperen
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