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Mult Scler. 2014 Jul;20(8):1033-41. doi: 10.1177/1352458513516529. Epub 2013 Dec 12.

Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis.

Author information

1
Centre for Information-Based Medicine, Hunter Medical Research Institute, Australia.
2
Griffith Health Institute, Griffith University, Australia Institute of Environmental Science and Research, New Zealand.
3
Centre for Information-Based Medicine, Hunter Medical Research Institute, Australia Griffith Health Institute, Griffith University, Australia.
4
Department of Immunology, Division of Medicine, John Hunter Hospital, Australia.
5
Faculty of Health Sciences and Medicine, Bond University, Australia.
6
Institute of Environmental Science and Research, New Zealand.
7
Centre for Information-Based Medicine, Hunter Medical Research Institute, Australia Division of Molecular Genetics, Hunter Area Pathology Service, Australia.
8
Centre for Information-Based Medicine, Hunter Medical Research Institute, Australia Department of Neurology, Division of Medicine, John Hunter Hospital, Australia Jeannette.lechner-scott@hnehealth.nsw.gov.au.

Abstract

BACKGROUND:

Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk of developing MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation are recognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure and inherited genetic systems.

OBJECTIVES AND METHODS:

To identify methylation changes associated with MS, we performed a genome-wide DNA methylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina 450K methylation arrays.

RESULTS:

A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. After prioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of a major effect CpG island in DRB1 in MS cases (pFDR < 3 × 10(-3)). In addition, we found 55 non-HLA CpGs that exhibited differential methylation, many of which localise to genes previously linked to MS.

CONCLUSIONS:

Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation to MS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.

KEYWORDS:

Epigenetics; genetics; immunology; methylation; multiple sclerosis

PMID:
24336351
DOI:
10.1177/1352458513516529
[Indexed for MEDLINE]

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