title: MTHFR functional genetic variation and methotrexate treatment response in rheumatoid arthritis: a meta-analysis.
abstract: OBJECTIVE
  To date, functional MTHFR SNPs have been tested for their impact on low-dose methotrexate (MTX) response in small rheumatoid arthritis (RA) cohorts. We sought to test their effect in the single largest cohort studied to date, and undertook a meta-analysis utilizing stringent study inclusion criteria.
  
  
  METHODS
  RA patients treated with MTX monotherapy from the Yorkshire Early Arthritis Register (YEAR) were genotyped using RFLP assays, and tested for association with treatment efficacy. Studies for meta-analysis were screened by a set of stringent inclusion criteria.
  
  
  CONCLUSIONS
  rs1801131 and rs1801133 were not associated with response to MTX in the YEAR cohort, nor did they affect the probability of achieving a low disease activity state. A meta-analysis of comparable studies found no association with these SNPs. MTHFR SNPs rs1801131 and rs1801133 are unlikely to have a clinically meaningful effect on the first 6 months of MTX treatment in early RA.
authors.affiliation: Leeds Institute of Rheumatic & Musculoskeletal Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Beckett Street, Leeds, West Yorkshire, LS9 7TF, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Morgan
authors.forename: Nashwa
authors.initials: N
authors.lastname: Al-Shaarawy
authors.forename: Steve
authors.initials: S
authors.lastname: Martin
authors.forename: James I
authors.initials: JI
authors.lastname: Robinson
authors.forename: Sarah
authors.initials: S
authors.lastname: Twigg
authors.forename: Awadalla A
authors.initials: AA
authors.lastname: Magdy
authors.forename: Aziza Sayed
authors.initials: AS
authors.lastname: Omar
authors.forename: Maivel H
authors.initials: MH
authors.lastname: Ghattas
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barrett
authors.forename: Ann W
authors.initials: AW
authors.lastname: Morgan
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D018501:Antirheumatic Agents; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate