OBJECTIVE: A systematic review and a meta-analysis were conducted, to investigate the possible association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with adverse effects related to methotrexate (MTX). METHODS: A systematic literature search in PubMed retrieved a total of 44 studies (42 unique articles). Two polymorphisms were included in the meta-analysis: C677T and A1298C. Random effect models were used in the analysis. Odds ratios along with their 95% confidence intervals were computed to compare the distribution of alleles and genotypes between cases and controls. RESULTS: The analysis highlighted a significant association of C677T polymorphism with overall MTX toxicity, hepatotoxicity, hematological toxicity, and neurotoxicity. It also revealed an association with MTX toxicity in patients with rheumatoid arthritis. In contrast, a protective effect of C677T MTHFR polymorphism on acute graft-versus-host disease and on patients treated with hematopoietic cell transplantation was found. As for the A1298C polymorphism, a statistically significant association with overall MTX toxicity and a protective role of the polymorphism in rheumatoid arthritis patients was detected. CONCLUSION: These results indicate the association of MTHFR polymorphisms with MTX toxicity. However, further studies are needed to reveal the underlying biological mechanism of the association.
OBJECTIVE: A systematic review and a meta-analysis were conducted, to investigate the possible association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with adverse effects related to methotrexate (MTX). METHODS: A systematic literature search in PubMed retrieved a total of 44 studies (42 unique articles). Two polymorphisms were included in the meta-analysis: C677T and A1298C. Random effect models were used in the analysis. Odds ratios along with their 95% confidence intervals were computed to compare the distribution of alleles and genotypes between cases and controls. RESULTS: The analysis highlighted a significant association of C677T polymorphism with overall MTXtoxicity, hepatotoxicity, hematological toxicity, and neurotoxicity. It also revealed an association with MTXtoxicity in patients with rheumatoid arthritis. In contrast, a protective effect of C677TMTHFR polymorphism on acute graft-versus-host disease and on patients treated with hematopoietic cell transplantation was found. As for the A1298C polymorphism, a statistically significant association with overall MTXtoxicity and a protective role of the polymorphism in rheumatoid arthritispatients was detected. CONCLUSION: These results indicate the association of MTHFR polymorphisms with MTXtoxicity. However, further studies are needed to reveal the underlying biological mechanism of the association.
Authors: Elena Nikiphorou; Andra Negoescu; John D Fitzpatrick; Calum T Goudie; Andrew Badcock; Andrew J K Östör; Anshuman P Malaviya Journal: Clin Rheumatol Date: 2014-03-09 Impact factor: 2.980