DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis.
Adult
Aged
Biomarkers
DNA Methylation
/ genetics
Diseases in Twins
/ blood
Enhancer Elements, Genetic
/ genetics
Epigenesis, Genetic
Epigenomics
/ methods
Female
Genetic Predisposition to Disease
Humans
Leukocytes, Mononuclear
Male
Membrane Proteins
/ genetics
Middle Aged
Multiple Sclerosis
/ blood
Promoter Regions, Genetic
/ genetics
Promyelocytic Leukemia Zinc Finger Protein
/ genetics
RNA, Long Noncoding
/ genetics
Twins, Monozygotic
Young Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 05 2019
07 05 2019
Historique:
received:
17
07
2018
accepted:
03
04
2019
entrez:
9
5
2019
pubmed:
9
5
2019
medline:
14
6
2019
Statut:
epublish
Résumé
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system with a modest concordance rate in monozygotic twins, which strongly argues for involvement of epigenetic factors. We observe highly similar peripheral blood mononuclear cell-based methylomes in 45 MS-discordant monozygotic twins. Nevertheless, we identify seven MS-associated differentially methylated positions (DMPs) of which we validate two, including a region in the TMEM232 promoter and ZBTB16 enhancer. In CD4 + T cells we find an MS-associated differentially methylated region in FIRRE. Additionally, 45 regions show large methylation differences in individual pairs, but they do not clearly associate with MS. Furthermore, we present epigenetic biomarkers for current interferon-beta treatment, and extensive validation shows that the ZBTB16 DMP is a signature for prior glucocorticoid treatment. Taken together, this study represents an important reference for epigenomic MS studies, identifies new candidate epigenetic markers, and highlights treatment effects and genetic background as major confounders.
Identifiants
pubmed: 31064978
doi: 10.1038/s41467-019-09984-3
pii: 10.1038/s41467-019-09984-3
pmc: PMC6504952
doi:
Substances chimiques
Biomarkers
0
Membrane Proteins
0
Promyelocytic Leukemia Zinc Finger Protein
0
RNA, Long Noncoding
0
TMEM232 protein, human
0
long noncoding RNA Firre, human
0
ZBTB16 protein, human
147855-37-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2094Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB-TR 128 SyNergy
Pays : International
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