SynthesisThe Journal of rheumatology2009
Metaanalysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity.
Synthesis in The Journal of rheumatology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 9 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 9 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- The impact of gene polymorphisms on the response of methotrexate-based treatments.European journal of clinical pharmacology · 2026Pooled it
- MTHFR gene polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis based on 16 studies.Clinical rheumatology · 2020Pooled it
- Genetic markers in methotrexate treatments.The pharmacogenomics journal · 2018Pooled it
- Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis.The pharmacogenomics journal · 2018Pooled it
- Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis.Scientific reports · 2017Pooled it
- Pooled it
- 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.The pharmacogenomics journal · 2013Pooled it
- Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Pooled it
- Outcomes related to methotrexate dose and route of administration in patients with rheumatoid arthritis: a systematic literature review.Clinical and experimental rheumatologyPooled it
- From Genotype to Functional Risk: A Multi-Omic Approach to Predicting Thiopurine and Methotrexate Co-Therapy-Induced Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Biomarkers of treatment response in rheumatoid arthritis: from conventional markers to tissue immunophenotype.Frontiers in immunology · 2026Review
- Drug-induced liver injury in inflammatory bowel disease: Challenges in diagnosis and monitoring.World journal of hepatology · 2025Review
- Severe hematologic toxicity after low-dose methotrexate in ectopic pregnancy: role of MTHFR polymorphism and drug interaction - a case report and literature review.Frontiers in pharmacology · 2025Article
- Pharmacogenetics of Drug Therapies in Rheumatoid Arthritis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Liver involvement in inflammatory bowel disease: What should the clinician know?World journal of hepatology · 2021Review
- Are There Any Ethnic Differences in the Response to Baricitinib for the Treatment of Rheumatoid Arthritis?Cureus · 2021Article
- Febrile neutropenia following with single-low-dose methotrexate for the treatment of ectopic pregnancy: a case report.The Pan African medical journal · 2021Article
- Severe Adverse Toxic Effects of Low-Dose Methotrexate Treatment on an Ectopic Pregnancy Patient With Methylenetetrahydrofolate Reductase Mutations: A Case Report.Frontiers in medicine · 2021Article
- Biomarkers to Personalize the Treatment of Rheumatoid Arthritis: Focus on Autoantibodies and Pharmacogenetics.Biomolecules · 2020Review
- Are gene polymorphisms related to adverse events of methotrexate in patients with rheumatoid arthritis? A retrospective cohort study based on an updated meta-analysis.Therapeutic advances in chronic disease · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
objectiveMethotrexate (MTX) is an effective therapy for rheumatoid arthritis (RA) but it is also associated with toxicity. Pharmacogenetics is the systematic evaluation of the role of genetic differences in the efficacy and toxicity of therapeutic interventions. Because the results of small pharmacogenetic studies are often misleading, we undertook a metaanalysis of published studies to determine the role of polymorphisms in the therapeutic efficacy and toxicity of MTX.
methodsA search of PubMed produced 55 publications, which were then reviewed for relevance to MTX toxicity and efficacy in patients with RA. To ensure that no study was missed, each polymorphism found was then entered as an independent search string and all results were reviewed again.
resultsOnly 2 polymorphisms [C677T and A1298C in methylenetetrahydrofolate reductase (MTHFR); total 8 studies] relevant to MTX metabolism and efficacy had sufficient data to allow a metaanalysis of their association with toxicity; there was no polymorphism with sufficient data to perform a metaanalysis of efficacy. In a fixed-effects model, the C677T polymorphism was associated with increased toxicity (OR 1.71, 95% CI 1.32-2.21, p < 0.001). The A1298C polymorphism was not associated with increased toxicity (OR 1.12, 95% CI 0.79-1.6, p = 0.626).
conclusionAs pharmacogenetics evolves, more data are needed to assess the role of various polymorphisms for drug efficacy and toxicity. These results illustrate the paucity of reliable pharmacogenetic data on a commonly used antirheumatic drug and the potential role of pharmacogenetics in tailoring drug therapy for an individual patient.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.