John R. Glossop
Genome-wide DNA methylation profiling in rheumatoid arthritis identifies disease-associated methylation changes that are distinct to individual T- and B-lymphocyte populations
Glossop, John R.; Emes, Richard D.; Nixon, Nicola B.; Haworth, Kim E.; Packham, Jon C.; Dawes, Peter T.; Fryer, Anthony A.; Mattey, Derek L.; Farrell, William E.
Authors
Richard D. Emes
Nicola B. Nixon
Kim E. Haworth
Jon C. Packham
Peter T. Dawes
Professor Anthony Fryer a.a.fryer@keele.ac.uk
Derek L. Mattey
William E. Farrell
Abstract
Changes to the DNA methylome have been described in patients with rheumatoid arthritis (RA). In previous work, we reported genome-wide methylation differences in T-lymphocyte and B-lymphocyte populations from healthy individuals. Now, using HumanMethylation450 BeadChips to interrogate genome-wide DNA methylation, we have determined disease-associated methylation changes in blood-derived T- and B-lymphocyte populations from 12 female patients with seropositive established RA, relative to 12 matched healthy individuals. Array data were analyzed using NIMBL software and bisulfite pyrosequencing was used to validate array candidates. Genome-wide DNA methylation, determined by analysis of LINE-1 sequences, revealed higher methylation in B-lymphocytes compared with T-lymphocytes (P ≤ 0.01), which is consistent with our findings in healthy individuals. Moreover, loci-specific methylation differences that distinguished T-lymphocytes from B-lymphocytes in healthy individuals were also apparent in RA patients. However, disease-associated methylation differences were also identified in RA. In these cases, we identified 509 and 252 CpGs in RA-derived T- and B-lymphocytes, respectively, that showed significant changes in methylation compared with their cognate healthy counterparts. Moreover, this included a restricted set of 32 CpGs in T-lymphocytes and 20 CpGs in B-lymphocytes (representing 15 and 10 genes, respectively, and including two, MGMT and CCS, that were common to both cell types) that displayed more substantial changes in methylation. These changes, apparent as hyper- or hypo-methylation, were independently confirmed by pyrosequencing analysis. Validation by pyrosequencing also revealed additional sites in some candidate genes that also displayed altered methylation in RA. In this first study of genome-wide DNA methylation in individual T- and B-lymphocyte populations in RA patients, we report disease-associated methylation changes that are distinct to each cell type and which support a role for discrete epigenetic regulation in this disease.
Citation
Glossop, J. R., Emes, R. D., Nixon, N. B., Haworth, K. E., Packham, J. C., Dawes, P. T., …Farrell, W. E. (2014). Genome-wide DNA methylation profiling in rheumatoid arthritis identifies disease-associated methylation changes that are distinct to individual T- and B-lymphocyte populations. Epigenetics, 9(9), 1228-1237. https://doi.org/10.4161/epi.29718
Journal Article Type | Article |
---|---|
Publication Date | 2014-09 |
Deposit Date | Aug 15, 2023 |
Journal | EPIGENETICS |
Print ISSN | 1559-2294 |
Publisher | Taylor and Francis |
Peer Reviewed | Peer Reviewed |
Volume | 9 |
Issue | 9 |
Pages | 1228-1237 |
DOI | https://doi.org/10.4161/epi.29718 |
PMID | 25147922 |
You might also like
Monitoring drug interventions in people with bipolar disorder
(2023)
Journal Article
Health Inequality and its link to HbA1c Test Recovery in a Developed Health Economy: In a 'Nearly Post COVID-19' World
(2022)
Presentation / Conference
Variability in test interval is linked to glycated haemoglobin (HbA1c) trajectory over time in people with diabetes
(2022)
Presentation / Conference
Downloadable Citations
About Keele Repository
Administrator e-mail: research.openaccess@keele.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search