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., Farrell, W. E., & 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
• Contract Date: Feb 27, 2017