The therapeutic response to D-penicillamine in rheumatoid arthritis: influence of glutathione S-transferase polymorphisms.
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.
Layton
M A
MA
Staffordshire Rheumatology Centre, Stoke-on-Trent, UK.
Jones
P W
PW
Alldersea
J E
JE
Strange
R C
RC
Fryer
A A
AA
Dawes
P T
PT
Mattey
D L
DL
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
D018501:Antirheumatic Agents; D012217:Rheumatoid Factor; D005982:Glutathione Transferase; D010396:Penicillamine