title: Are gene polymorphisms related to treatment outcomes of methotrexate in patients with rheumatoid arthritis? A systematic review and meta-analysis.
abstract: OBJECTIVE
  Identifying the predictors of responsiveness and adverse events in methotrexate (MTX) treated patients with rheumatoid arthritis (RA) has been the focus of most concern, but still without consistent consensus.
  
  
  METHODS
  PubMed and OVID EMBASE were searched to collect relevant studies that addressed correlations between gene polymorphisms and efficacy and/or toxicity in MTX-treated RA patients. Allelic, recessive, dominant and over-dominant model were applied.
  
  
  RESULTS
  A total of 68 studies were included. For associations with efficacy, AMPD1 34C>T polymorphism was related to responsiveness in dominant model (odds ratio [OR]: 1.77; 95% CI: 1.19-2.63) and over-dominant model (OR: 1.59; 95% CI: 1.04-2.45). ATIC T675C polymorphism had association with responsiveness in recessive model (OR: 2.54; 95% CI: 1.23-5.26). For associations with toxicity, polymorphisms in TYMS 1494 del6 and FPGS rs10106 were correlated to absenting overall adverse events in recessive model (OR: 0.68; 95% CI: 0.49-0.95) and dominant model (OR: 0.54; 95% CI: 0.35-0.83) respectively while MTHFR C677T was associated with presenting overall adverse events in allelic model (OR: 1.29; 95% CI: 1.02-1.63), recessive model (OR: 1.38; 95% CI: 1.00-1.89) and dominant model (OR: 1.41; 95% CI: 1.02-1.94).
  
  
  CONCLUSIONS
  Polymorphisms in AMPD1 34C>T and ATIC T675C predict responsiveness. The absence of TYMS 1494 del6 and FPGS rs10106 and presence of MTHFR C677T predict adverse events in RA patients treated with MTX. Moreover, variations of the associations were found between Caucasians and non-Caucasians.
authors.affiliation: Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Record & Statistics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science & Technology, Chengdu, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zou
authors.affiliation: Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Rheumatology & Immunology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate
keywords: efficacy; meta-analysis; methotrexate; polymorphisms; rheumatoid arthritis; toxicity