title: DNA methylation at diagnosis is associated with response to disease-modifying drugs in early rheumatoid arthritis.
abstract: 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).
  
  
  
  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.
  
  
  
  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).
  
  
  
  DNA methylation at diagnosis is associated with disease-modifying antirheumatic drug treatment response in early RA.
authors.affiliation: Guy Hilton Research Centre, Institute for Applied Clinical Sciences, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.|Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Glossop
authors.affiliation: Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK.
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Nixon
authors.affiliation: School of Veterinary Medicine & Science, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, LE12 5RD, UK.|Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, LE12 5RD, UK.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Emes
authors.affiliation: School of Health & Rehabilitation, Keele University, Staffordshire, ST5 5BG, UK.
authors.forename: Julius
authors.initials: J
authors.lastname: Sim
authors.affiliation: Guy Hilton Research Centre, Institute for Applied Clinical Sciences, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.|Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK.
authors.forename: Jon C
authors.initials: JC
authors.lastname: Packham
authors.affiliation: Guy Hilton Research Centre, Institute for Applied Clinical Sciences, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.|Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK.
authors.forename: Derek L
authors.initials: DL
authors.lastname: Mattey
authors.affiliation: Guy Hilton Research Centre, Institute for Applied Clinical Sciences, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.
authors.forename: William E
authors.initials: WE
authors.lastname: Farrell
authors.affiliation: Guy Hilton Research Centre, Institute for Applied Clinical Sciences, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fryer
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents
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