title: The therapeutic response to D-penicillamine in rheumatoid arthritis: influence of glutathione S-transferase polymorphisms.
abstract: OBJECTIVE
  To investigate whether the therapeutic response of rheumatoid arthritis (RA) patients to D-penicillamine is associated with polymorphisms in genes of the glutathione S-transferase (GST) supergene family.
  
  
  METHODS
  Disease activity in 81 patients with RA treated with D-penicillamine monotherapy was assessed using the Stoke Index, a validated index of disease activity, prior to treatment and at 6 months. GST typing was performed using a polymerase chain reaction-based approach and a logistic regression model was used to investigate any possible association between the therapeutic response to D-penicillamine and the GST genotype.
  
  
  RESULTS
  A poor therapeutic response was associated with the GSTM1 null genotype [odds ratio (OR) 3.94], and in particular with the GSTM1*0/GSTM3*A haplotype (OR 7.63).
  
  
  CONCLUSIONS
  Our results suggest that GST polymorphisms may influence the response to D-penicillamine in RA, and that patients in possession of the GSTM1*0/GSTM3*A haplotype are significantly less likely to show a beneficial response to the drug.
authors.affiliation: Staffordshire Rheumatology Centre, Stoke-on-Trent, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Layton
authors.forename: P W
authors.initials: PW
authors.lastname: Jones
authors.forename: J E
authors.initials: JE
authors.lastname: Alldersea
authors.forename: R C
authors.initials: RC
authors.lastname: Strange
authors.forename: A A
authors.initials: AA
authors.lastname: Fryer
authors.forename: P T
authors.initials: PT
authors.lastname: Dawes
authors.forename: D L
authors.initials: DL
authors.lastname: Mattey
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010396:Penicillamine / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D012217:Rheumatoid Factor; D005982:Glutathione Transferase; D010396:Penicillamine