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MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms

MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid... Association of two key variants mapping to the MTHFR gene (C677T (rs1801133) and A1298C (rs1801131)) with response to methotrexate (MTX) remains controversial. We investigated these and other markers spanning the gene as predictors of MTX efficacy and adverse events in a UK rheumatoid arthritis (RA) patient cohort and performed a meta-analysis of the two key variants using all published data. The tagging single nucleotide polymorphisms (SNPs) were genotyped in 309 patients with well-defined outcomes to MTX treatment and 17 studies were included in the meta-analysis. No association of the SNPs tested was detected with MTX efficacy or toxicity in our UK cohort. After combining our data with previous studies by meta-analysis, the random effects pooled odds ratios (OR) for both C677T and A1298C showed no association with efficacy or toxicity for either of the SNPs (efficacy: OR=1.05 (95% confidence interval (CI) 0.83–1.32) and OR=0.81 (95% CI 0.53–1.24), respectively; toxicity: OR=1.38 (95% CI 0.90–2.12) and OR=1.19 (95% CI 0.80–1.78), respectively). The available evidence suggests that the MTHFR C677T and A1298C gene polymorphisms are not reliable predictors of response to MTX treatment in RA patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Pharmacogenomics Journal Springer Journals

MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms

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References (66)

Publisher
Springer Journals
Copyright
Copyright
Subject
Biomedicine; Biomedicine, general; Human Genetics; Pharmacotherapy; Gene Expression; Oncology; Psychopharmacology
ISSN
1470-269X
eISSN
1473-1150
DOI
10.1038/tpj.2011.42
Publisher site
See Article on Publisher Site

Abstract

Association of two key variants mapping to the MTHFR gene (C677T (rs1801133) and A1298C (rs1801131)) with response to methotrexate (MTX) remains controversial. We investigated these and other markers spanning the gene as predictors of MTX efficacy and adverse events in a UK rheumatoid arthritis (RA) patient cohort and performed a meta-analysis of the two key variants using all published data. The tagging single nucleotide polymorphisms (SNPs) were genotyped in 309 patients with well-defined outcomes to MTX treatment and 17 studies were included in the meta-analysis. No association of the SNPs tested was detected with MTX efficacy or toxicity in our UK cohort. After combining our data with previous studies by meta-analysis, the random effects pooled odds ratios (OR) for both C677T and A1298C showed no association with efficacy or toxicity for either of the SNPs (efficacy: OR=1.05 (95% confidence interval (CI) 0.83–1.32) and OR=0.81 (95% CI 0.53–1.24), respectively; toxicity: OR=1.38 (95% CI 0.90–2.12) and OR=1.19 (95% CI 0.80–1.78), respectively). The available evidence suggests that the MTHFR C677T and A1298C gene polymorphisms are not reliable predictors of response to MTX treatment in RA patients.

Journal

The Pharmacogenomics Journal – Springer Journals

Published: Sep 20, 2011

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