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

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 treatmen...

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Main Authors: Glossop, John R., Nixon, Nicola B., Emes, Richard D., Sim, Julius, Packman, Jon C., Mattey, Derek L., Farrell, William E., Fryer, Anthony A.
Format: Article
Published: Future Medicine 2016
Online Access:https://eprints.nottingham.ac.uk/40090/
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author Glossop, John R.
Nixon, Nicola B.
Emes, Richard D.
Sim, Julius
Packman, Jon C.
Mattey, Derek L.
Farrell, William E.
Fryer, Anthony A.
author_facet Glossop, John R.
Nixon, Nicola B.
Emes, Richard D.
Sim, Julius
Packman, Jon C.
Mattey, Derek L.
Farrell, William E.
Fryer, Anthony A.
author_sort Glossop, John R.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-400902020-05-04T18:19:56Z https://eprints.nottingham.ac.uk/40090/ 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. 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. Future Medicine 2016-11-25 Article PeerReviewed Glossop, John R., Nixon, Nicola B., Emes, Richard D., Sim, Julius, Packman, Jon C., Mattey, Derek L., Farrell, William E. and Fryer, Anthony A. (2016) DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis. Epigenomics . ISSN 1750-192X http://www.futuremedicine.com/doi/10.2217/epi-2016-0042 doi:10.2217/epi-2016-0042 doi:10.2217/epi-2016-0042
spellingShingle Glossop, John R.
Nixon, Nicola B.
Emes, Richard D.
Sim, Julius
Packman, Jon C.
Mattey, Derek L.
Farrell, William E.
Fryer, Anthony A.
DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis
title DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis
title_full DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis
title_fullStr DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis
title_full_unstemmed DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis
title_short DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis
title_sort dna methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis
url https://eprints.nottingham.ac.uk/40090/
https://eprints.nottingham.ac.uk/40090/
https://eprints.nottingham.ac.uk/40090/