TYMS polymorphisms and responsiveness to or toxicity of methotrexate in rheumatoid arthritis.

Abstract

The aim of this study was to investigate whether the thymidylate synthase (TYMS) 2R/3R and 6 bpI/D polymorphisms can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). We conducted ameta-analysis of studies on the association between the TYMS 2R/3R and 6 bpI/D polymorphisms and non-responsiveness to or toxicity of MTX in RA patients. Atotal of 11studies involving 1613patients were considered. Meta-analysis showed no association between the TYMS 2R/3R 3R allele and non-responsiveness to MTX therapy (odds ratio [OR] = 1.087, confidence interval [CI] = 0.682-1.731, p = 0.726). The meta-analysis indicated that there was no association between the TYMS 6 bpI/DD allele and non-responsiveness to MTX therapy (OR = 0.688, 95% CI = 0.281-1.683, p = 0.413). Meta-analysis revealed that the TYMS 2R/3R polymorphism was not associated with MTX toxicity, except for in aco-dominant model, and the TYMS 6 bpI/D polymorphism was not associated with MTX toxicity in all genetic models. This meta-analysis demonstrates that the TYMS 2R/3R and 6 bpI/D polymorphisms may not be associated with non-responsiveness to or toxicity of MTX therapy in RA patients.