SynthesisClinical rheumatology2014
Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis.
Synthesis in Clinical rheumatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 7 of them syntheses that pooled it.
What it found
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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
26 citing papers in PubMed, 7 syntheses or guidelines pooled it, 46 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
- Associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with genetic susceptibility to rheumatoid arthritis: a meta-analysis.Clinical rheumatology · 2017Pooled it
- Genetics are not likely to offer clinically useful predictions for elevated liver enzyme levels in patients using low dose methotrexate.Seminars in arthritis and rheumatism · 2022Trial
- Case 22: A 65-Year-Old-Woman With Neutropenia.Journal of Korean medical science · 2026Article
- Gene polymorphisms associated with immunosuppressant adverse effects in systemic lupus erythematosus: a narrative review.Frontiers in genetics · 2025Review
- Comparison of the efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials.Zeitschrift fur Rheumatologie · 2024Article
- Relative remission rates of Janus kinase inhibitors in comparison with adalimumab in patients with active rheumatoid arthritis: a network meta-analysis.Zeitschrift fur Rheumatologie · 2024Article
- Comparison of the efficacy and safety of tocilizumab, sarilumab, and olokizumab in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials.Zeitschrift fur Rheumatologie · 2024Article
- Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs.Zeitschrift fur Rheumatologie · 2021Article
- Biomarkers to Personalize the Treatment of Rheumatoid Arthritis: Focus on Autoantibodies and Pharmacogenetics.Biomolecules · 2020Review
- Relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison to adalimumab in patients with active rheumatoid arthritis.Zeitschrift fur Rheumatologie · 2020Article
- Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia.Iranian journal of basic medical sciences · 2020Article
- 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
- Effects of Methylene Tetrahydro Folate Reductase Gene Polymorphisms on Methotrexate Toxicity in Egyptian Pediatric Acute Lymphocytic Leukaemia Patients.Iranian journal of pharmaceutical research : IJPR · 2020Article
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to explore whether the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) play a role in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). MEDLINE and EMBASE database searches and subsequent manual searches were utilized to identify articles in which C677T and A1298C MTHFR polymorphisms were evaluated in RA patients taking MTX. A meta-analysis was conducted to identify associations between MTHFR polymorphisms and MTX toxicity. Twelve studies comprising a total of 2,288 RA patients were included in our meta-analysis. Meta-analysis revealed an association between the overall toxicity of MTX and the MTHFR 677TT genotype (odds ratio [OR] = 1.615, 95 % confidence interval [CI] = 1.185-2.200, p = 0.002). Stratification by ethnicity indicated an association between the MTHFR 677TT genotype and the overall toxicity of MTX in East Asians (OR = 1.583, 95 % CI = 1.075-2.331, p = 0.020). The toxicity of MTX also was found to be associated with the TT genotype in patients taking folate (OR = 1.893, 95 % CI = 1.283-2.793, p = 0.001). Stratification by toxicity type indicated an association between the MTHFR 677TT genotype and any adverse effects (OR = 1.716, 95 % CI = 1.127-2.612, p = 0.012). Meta-analysis stratified by toxicity type indicated an association between the MTHFR 1298CC genotype and any adverse effects (OR = 0.501, 95 % CI = 0.284-0.886, p = 0.017). The results of our meta-analysis suggest that the MTHFR C677T and A1298C polymorphisms are associated with MTX toxicity in RA patients.
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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.