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 Lopez; 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 Lopez, Fredrik Piehl, Maja Jagodic

Centre for Host Microbiome Interactions

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

39 Citations (Scopus)

184 Downloads (Pure)

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.

Original language	English
Number of pages	13
Journal	Multiple sclerosis (Houndmills, Basingstoke, England)
Early online date	2 Aug 2017
DOIs	https://doi.org/10.1177/1352458517721356
Publication status	E-pub ahead of print - 2 Aug 2017

Access to Document

10.1177/1352458517721356Licence: CC BY

Hypermethylation of MIR21 in_RUHRMANN_Firstpublished2August2017_GOLD VoR (CC BY)Final published version, 996 KBLicence: CC BY

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 Lopez, 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 (Houndmills, Basingstoke, England). Advance online publication. https://doi.org/10.1177/1352458517721356

@article{30d3a428683e418885bac88568142215,

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 = "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.",

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 {Gomez Cabrero Lopez}, David and Fredrik Piehl and Maja Jagodic",

year = "2017",

month = aug,

day = "2",

doi = "10.1177/1352458517721356",

language = "English",

journal = "Multiple sclerosis (Houndmills, Basingstoke, England)",

issn = "1477-0970",

publisher = "Sage Publications",

}

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 Lopez, 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 (Houndmills, Basingstoke, England). 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 (Houndmills, Basingstoke, England), 02.08.2017.

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 Lopez, David

AU - Piehl, Fredrik

AU - Jagodic, Maja

PY - 2017/8/2

Y1 - 2017/8/2

N2 - 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.

AB - 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.

U2 - 10.1177/1352458517721356

DO - 10.1177/1352458517721356

M3 - Article

C2 - 28766461

SN - 1477-0970

JO - Multiple sclerosis (Houndmills, Basingstoke, England)

JF - Multiple sclerosis (Houndmills, Basingstoke, England)

ER -

Ruhrmann S, Ewing E, Piket E, Kular L, Cetrulo Lorenzi JC, Fernandes SJ et al. 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 (Houndmills, Basingstoke, England). 2017 Aug 2. Epub 2017 Aug 2. 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

Abstract

Access to Document

Fingerprint

Cite this