Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis
Description
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.
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ID Code: | 109954 | ||
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Item Type: | Contribution to Journal (Journal Article) | ||
Refereed: | Yes | ||
ORCID iD: |
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Measurements or Duration: | 9 pages | ||
Keywords: | Epigenetics, genetics, immunology, methylation, multiple sclerosis | ||
DOI: | 10.1177/1352458513516529 | ||
ISSN: | 1477-0970 | ||
Pure ID: | 32764134 | ||
Divisions: | Past > QUT Faculties & Divisions > Faculty of Health Past > Institutes > Institute of Health and Biomedical Innovation |
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Copyright Owner: | Consult author(s) regarding copyright matters | ||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||
Deposited On: | 18 Aug 2017 03:07 | ||
Last Modified: | 07 Aug 2024 14:33 |
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