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

Moira C. Graves, Miles C. Benton, R. A. Lea, Frances M. Boyle, L. Tajouri, D. Macartney-Coxson, Rodney J. Scott, Jeannette Lechner-Scott

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Abstract

Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation arerecognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure andinherited genetic systems.Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNAmethylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina450K methylation arrays.Results: A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. Afterprioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of amajor effect CpG island in DRB1 in MS cases (pFDR <3 x 10-3). In addition, we found 55 non-HLA CpGs that exhibiteddifferential 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 toMS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.

Original languageEnglish
Pages (from-to)1033-1041
Number of pages9
JournalMultiple Sclerosis
Volume20
Issue number8
DOIs
Publication statusPublished - 2014

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    Graves, M. C., Benton, M. C., Lea, R. A., Boyle, F. M., Tajouri, L., Macartney-Coxson, D., Scott, R. J., & Lechner-Scott, J. (2014). Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis. Multiple Sclerosis, 20(8), 1033-1041. https://doi.org/10.1177/1352458513516529