DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis

Glossop, John R.; Nixon, Nicola B.; Emes, Richard D.; Sim, Julius; Packman, Jon C.; Mattey, Derek L.; Farrell, William E.; Fryer, Anthony A.

Abstract

Aim: A proof-of-concept study to explore whether DNA methylation at first diagnosis is associated with response to disease-modifying antirheumatic drugs (DMARDs) in patients with early rheumatoid arthritis (RA). Patients & methods: DNA methylation was quantified in T-lymphocytes from 46 treatment-naive patients using HumanMethylation450 BeadChips. Treatment response was determined in 6 months using the European League Against Rheumatism (EULAR) response criteria. Results: Initial filtering identified 21 cytosine-phosphate-guanines (CpGs) that were differentially methylated between responders and nonresponders. After conservative adjustment for multiple testing, six sites remained statistically significant, of which four showed high sensitivity and/or specificity (≥75%) for response to treatment. Moreover, methylation at two sites in combination was the strongest factor associated with response (80.0% sensitivity, 90.9% specificity, AUC 0.85). Conclusion: DNA methylation at diagnosis is associated with disease-modifying antirheumatic drug treatment response in early RA.

Citation

Glossop, J. R., Nixon, N. B., Emes, R. D., Sim, J., Packman, J. C., Mattey, D. L., …Fryer, A. A. (2016). DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis. Epigenomics, 9(4), https://doi.org/10.2217/epi-2016-0042

• Journal Article Type: Article
• Acceptance Date: Oct 12, 2016
• Publication Date: Nov 25, 2016
• Deposit Date: Feb 27, 2017
• Publicly Available Date: Feb 27, 2017
• Journal: Epigenomics
• Print ISSN: 1750-1911
• Electronic ISSN: 1750-192X
• Publisher: Future Medicine
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 4
• DOI: https://doi.org/10.2217/epi-2016-0042
• Keywords: disease activity score with 28 joint counts (DAS28); disease-modifying antirheumatic drugs (DMARDs); DNA methylation; early rheumatoid arthritis; Illumina 450K array; T-lymphocyte; treatment response
• Public URL: https://nottingham-repository.worktribe.com/output/826949
• Publisher URL: http://www.futuremedicine.com/doi/10.2217/epi-2016-0042
• Additional Information: For full bibliographic citation, please refer to the version available at www.future-science.com