- Title
- Differential methylation at MHC in CD4⁺ T cells is associated with multiple sclerosis independently of HLA-DRB1
- Creator
- Maltby, Vicki E.; Lea, Rodney A.; Sanders, Katherine A.; White, Nicole; Benton, Miles C.; Scott, Rodney J.; Lechner-Scott, Jeannette
- Relation
- Clinical Epigenetics Vol. 9, no. 71
- Publisher Link
- http://dx.doi.org/10.1186/s13148-017-0371-1
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2017
- Description
- Background: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how these variants contribute to disease. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. In a previous study, we found a differentially methylation region (DMR) at MHC HLA-DRB1 that was associated within relapsing-remitting MS (RRMS) patients in CD4⁺ T cells. This study aimed to confirm this earlier finding in an independent RRMS cohort of treatment-naive female patients. Methods: Total genomic DNA was extracted from CD4⁺ T cells of 28 female RRMS and 22 age-matched healthy controls subjects. DNA was bisulfite-converted and hybridised to Illumina 450K arrays. Beta values for all CpGs were analysed using the DMPFinder function in the MINFI program, and a follow-up prioritisation process was applied to identify the most robust MS-associated DMRs. Results: This study confirmed our previous findings of a hypomethylated DMR at HLA-DRB1 and a hypermethylated DMR at HLA-DRB5 in this RRMS patient cohort. In addition, we identified a large independent DMR at MHC, whereby 11 CpGs in RNF39 were hypermethylated in MS cases compared to controls (max. Δbeta = 0.19, P = 2.1 × 10-4). We did not find evidence that SNP genotype was influencing the DMR in this cohort. A smaller MHC DMR was also identified at HCG4B, and two non-MHC DMRs at PM20D1 on chr1 and ERICH1 on chr8 were also identified. Conclusions: The findings from this study confirm our previous results of a DMR at HLA-DRB1 and also suggest hypermethylation in an independent MHC locus, RNF39, is associated with MS. Taken together, our results highlight the importance of epigenetic factors at the MHC locus in MS independent of treatment, age and sex. Prospective studies are now required to discern whether methylation at MHC is involved in influencing risk of disease onset or whether the disease itself has altered the methylation profile.
- Subject
- multiple sclerosis; genetics; methylation; gene expression; environmental factors
- Identifier
- http://hdl.handle.net/1959.13/1395079
- Identifier
- uon:33809
- Identifier
- ISSN:1868-7075
- Rights
- © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Language
- eng
- Full Text
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