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Glutathione S-Transferase Gene Polymorphisms as Predictors of Methotrexate Efficacy in Juvenile Idiopathic Arthritis
Sanda Huljev Frkovic1, Marija Jelusic1, Kristina Crkvenac Gornik2
1Department of Paediatrics, University Hospital Centre Zagreb, University of Zagreb School of Medicine, 10000 Zagreb, Croatia.
Abstract:
Because of the unpredictable efficacy of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA), the possibility of a favourable outcome is reduced in more than 30% of patients. To investigate the possible influence of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene deletion polymorphisms on MTX efficacy in patients with JIA, we determined these polymorphisms in 63 patients with JIA who did not achieve remission and 46 patients with JIA who achieved remission during MTX therapy. No significant differences were observed in the distribution of single GSTM1 or GSTT1 deletion polymorphisms or their combination between the two groups: 58.7% to 63.5%; p = 0.567, 17.4% to 22.2%; p = 0.502, and 13% to 12.7%; p = 0.966, respectively. Our results suggest that GSTM1 and GSTT1 deletion polymorphisms do not influence the efficacy of MTX in patients with JIA. Additional studies are required to determine the possible influence of GST deletion polymorphisms on MTX efficacy in patients with JIA.
Insights
Glutathione S-transferase (GST) gene deletions do not appear to impact methotrexate treatment effectiveness in juvenile idiopathic arthritis (JIA). Further research is needed to confirm these findings for GSTM1 and GSTT1 polymorphisms in JIA patients.
Area of Science:
- Pharmacogenetics
- Immunology
- Pediatric Rheumatology
Background:
- Methotrexate (MTX) efficacy in juvenile idiopathic arthritis (JIA) is unpredictable, affecting over 30% of patients.
- Genetic factors may influence individual responses to MTX therapy in JIA.
- Glutathione S-transferase (GST) enzymes play a role in drug metabolism.
Purpose of the Study:
- To investigate the association between glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene deletion polymorphisms and MTX efficacy in JIA patients.
- To determine if specific GST gene polymorphisms predict treatment outcomes in JIA.
Main Methods:
- Genotyping for GSTM1 and GSTT1 deletion polymorphisms was performed.
- Polymorphism distribution was compared between JIA patients who achieved MTX remission and those who did not.
- A cohort of 63 non-remission and 46 remission JIA patients was analyzed.
Main Results:
- No significant differences in the frequency of GSTM1 deletion polymorphisms were observed between remission and non-remission groups (58.7% vs. 63.5%, p=0.567).
- No significant differences in the frequency of GSTT1 deletion polymorphisms were observed between remission and non-remission groups (17.4% vs. 22.2%, p=0.502).
- Combined GSTM1 and GSTT1 deletion polymorphisms also showed no significant difference between the groups (13% vs. 12.7%, p=0.966).
Conclusions:
- GSTM1 and GSTT1 deletion polymorphisms do not appear to influence MTX efficacy in patients with JIA.
- These specific genetic variations are unlikely to be major predictors of MTX treatment response in this population.
- Further investigation into other genetic or environmental factors influencing MTX efficacy in JIA is warranted.
