John R Glossop1,2, Nicola B Nixon2, Richard D Emes3,4, Julius Sim5, Jon C Packham1,2, Derek L Mattey1,2, William E Farrell1, Anthony A Fryer1. 1. Guy Hilton Research Centre, Institute for Applied Clinical Sciences, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK. 2. Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK. 3. School of Veterinary Medicine & Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, LE12 5RD, UK. 4. Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, LE12 5RD, UK. 5. School of Health & Rehabilitation, Keele University, Staffordshire, ST5 5BG, UK.
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.
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.
Entities:
Keywords:
DNA methylation; Illumina 450K array; T-lymphocyte; disease activity score with 28 joint counts (DAS28); disease-modifying antirheumatic drugs (DMARDs); early rheumatoid arthritis; treatment response
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