Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis.

Abstract

This study investigated whether the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) 347 C/G polymorphism can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between ATIC 347 C/G polymorphism and non-responsiveness to or toxicity of MTX in RA patients, using PUBMED, EMBASE, and COCHRANE. Nine comparative studies from 6 articles including 1056 RA patients met our inclusion criteria. This final group of studies comprised 5 studies on response to MTX and 4 on toxicity of MTX in RA patients in relation to the ATIC 347 C/G polymorphism status. Meta-analysis showed association between the ATIC 347 GG+GC genotype and non-response to MTX therapy (OR=1.572, 95% CI 1.146-2.156, p=0.005). Stratification by ethnicity indicated significant association between the ATIC 347 GG+GC genotype and non-response to MTX in Caucasians (OR=1.884, 95% CI 1.236-2.873, p=0.003), but not in Asian patients. Similarly, associations were noted for the ATIC 347 C/G polymorphism through analysis using recessive and overdominant models. Meta-analysis revealed association between the ATIC 347 GG+GC genotype and MTX toxicity (OR=1.454 95% CI 1.034-2.044, p=0.032). Stratification by ethnicity indicated significant association between the ATIC 347 GG+GC genotype and MTX toxicity in Caucasians (OR=1.741, 95% CI 1.080-2.806, p=0.023), but not in Asian patients. The ATIC 347 C/G polymorphism may be associated with non-responsiveness to and or toxicity of MTX in Caucasian RA patients.