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

Sabrina Ruhrmann; Ewoud Ewing; Eliane Piket; Lara Kular; Julio Cesar Cetrulo Lorenzi; Sunjay Jude Fernandes; Hiromasa Morikawa; Shahin Aeinehband; Sergi Sayols-Baixeras; Stella Aslibekyan; Devin M Absher; Donna K Arnett; Jesper Tegner; David Gomez-Cabrero; Fredrik Piehl; Maja Jagodic

doi:10.1177/1352458517721356

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

Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M Absher, Donna K Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1288-1300
Number of pages	13
Journal	Multiple Sclerosis Journal
Volume	24
Issue number	10
DOIs	https://doi.org/10.1177/1352458517721356
State	Published - Aug 2 2017
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: 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.

Access to Document

10.1177/1352458517721356

https://repository.kaust.edu.sa/bitstream/10754/625313/1/1352458517721356.pdf

Cite this

Ruhrmann, S., Ewing, E., Piket, E., Kular, L., Cetrulo Lorenzi, J. C., Fernandes, S. J., Morikawa, H., Aeinehband, S., Sayols-Baixeras, S., Aslibekyan, S., Absher, D. M., Arnett, D. K., Tegner, J., Gomez-Cabrero, D., Piehl, F., & Jagodic, M. (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, 24(10), 1288-1300. https://doi.org/10.1177/1352458517721356

@article{239e5213468b4ed29e49dbe984cca8a8,

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",

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.",

author = "Sabrina Ruhrmann and Ewoud Ewing and Eliane Piket and Lara Kular and {Cetrulo Lorenzi}, {Julio Cesar} and Fernandes, {Sunjay Jude} and Hiromasa Morikawa and Shahin Aeinehband and Sergi Sayols-Baixeras and Stella Aslibekyan and Absher, {Devin M} and Arnett, {Donna K} and Jesper Tegner and David Gomez-Cabrero and Fredrik Piehl and Maja Jagodic",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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.",

year = "2017",

month = aug,

day = "2",

doi = "10.1177/1352458517721356",

language = "English (US)",

volume = "24",

pages = "1288--1300",

journal = "Multiple Sclerosis Journal",

issn = "1352-4585",

publisher = "SAGE Publications Ltd",

number = "10",

}

Ruhrmann, S, Ewing, E, Piket, E, Kular, L, Cetrulo Lorenzi, JC, Fernandes, SJ, Morikawa, H, Aeinehband, S, Sayols-Baixeras, S, Aslibekyan, S, Absher, DM, Arnett, DK, Tegner, J, Gomez-Cabrero, D, Piehl, F & Jagodic, M 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, vol. 24, no. 10, pp. 1288-1300. https://doi.org/10.1177/1352458517721356

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. / Ruhrmann, Sabrina; Ewing, Ewoud; Piket, Eliane et al.
In: Multiple Sclerosis Journal, Vol. 24, No. 10, 02.08.2017, p. 1288-1300.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Ruhrmann, Sabrina

AU - Ewing, Ewoud

AU - Piket, Eliane

AU - Kular, Lara

AU - Cetrulo Lorenzi, Julio Cesar

AU - Fernandes, Sunjay Jude

AU - Morikawa, Hiromasa

AU - Aeinehband, Shahin

AU - Sayols-Baixeras, Sergi

AU - Aslibekyan, Stella

AU - Absher, Devin M

AU - Arnett, Donna K

AU - Tegner, Jesper

AU - Gomez-Cabrero, David

AU - Piehl, Fredrik

AU - Jagodic, Maja

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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.

PY - 2017/8/2

Y1 - 2017/8/2

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/625313

UR - http://journals.sagepub.com/doi/10.1177/1352458517721356

UR - http://www.scopus.com/inward/record.url?scp=85029581966&partnerID=8YFLogxK

U2 - 10.1177/1352458517721356

DO - 10.1177/1352458517721356

M3 - Article

C2 - 28766461

SN - 1352-4585

VL - 24

SP - 1288

EP - 1300

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 10

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this