The therapeutic response to D-penicillamine in rheumatoid arthritis: influence of glutathione S-transferase polymorphisms

Objectives. To investigate whether the therapeutic response of rheumatoid a rthritis (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-penicillami ne monotherapy was assessed using the Stoke Index, a validated index of dis ease 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 therape utic response to D-penicillamine and the GST genotype. Results. A poor therapeutic response was associated with the GSTM1 null gen otype [odds ratio (OR) 3.94], and in particular with the GSTM1*0/GSTM3*A ha plotype (OR 7.63). Conclusions. Our results suggest that CST polymorphisms may influence the r esponse to D-penicillamine in RE, and that patients in possession of the GS TM1*0/GSTM3*A haplotype are significantly less likely to show a beneficial response to the drug.