title: Association of the ABCB1 C3435T polymorphism with responsiveness to and toxicity of DMARDs in rheumatoid arthritis : A meta-analysis.
abstract: OBJECTIVE
  The aim of this study was to investigate whether the C3435T polymorphism in the gene encoding multidrug resistance protein 1 (ABCB1) can predict responsiveness to or toxicity of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  We conducted a meta-analysis of studies on the association between the ABCB1 C3435T polymorphism and nonresponsiveness to or toxicity of DMARDs in RA patients, using the PUBMED and EMBASE electronic citation databases. Subsequent inclusion/exclusion procedures were performed and then data were extracted for association analysis.
  
  
  RESULTS
  A total of 14 comparison studies from 9 articles met our inclusion criteria. This final group comprised 4 studies containing data on associations between the ABCB1 C3435T polymorphism and RA susceptibility, 5 studies on the response to DMARDs, and 5 on toxicity of DMARDs in RA patients according to ABCB1 polymorphism status. Meta-analysis revealed no association between RA susceptibility and the ABCB1 C3435T polymorphism [odds ratio (OR) for the T allele = 0.948, 95 % confidence interval (CI) 0.756-1.189, p = 0.645]. Meta-analysis showed no association between the ABCB1 C3435T T allele and a nonresponse to DMARD therapy (OR 0.952, 95 % CI 0.516-1.685, p = 0.817). Stratification by DMARD type indicated no association between the ABCB1 C3435T T allele and nonresponse to methotrexate (MTX) treatment (OR 1.201, 95 % CI  0.456-3.164, p = 0.711). However, the analysis did indicate that MTX toxicity was associated with the ABCB1 C3435T polymorphism in RA under an overdominant model (TC vs. TT + CC; OR 0.483, 95 % CI 0.259-0.900, p = 0.022), evidencing a lower risk of MTX toxicity for heterozygotes (TC) than homozygotes (TT and CC).
  
  
  CONCLUSIONS
  This meta-analysis demonstrated that the ABCB1 C3435T polymorphism may be not associated with responsiveness to DMARD therapy, but may be associated with MTX toxicity in RA.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 136-705, Seoul, Korea. lyhcgh@korea.ac.kr.
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
authors.forename: S-C
authors.initials: SC
authors.lastname: Bae
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 136-705, Seoul, Korea.
authors.forename: G G
authors.initials: GG
authors.lastname: Song
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D018501:Antirheumatic Agents; D005819:Genetic Markers
keywords: Autoimmune diseases; Disease-modifying, antirheumatic drugs; Methotrexate; Polymorphism, genetic; Side effects