ArticlePediatric rheumatology online journal2016
Mutations in the MTHFR gene are not associated with Methotrexate intolerance in patients with juvenile idiopathic arthritis.
Article in Pediatric rheumatology online journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetic markers in methotrexate treatments.The pharmacogenomics journal · 2018Pooled it
- Conservative Methotrexate Management of Ovarian Ectopic Pregnancy in a Resource-Constrained Setting: A Rare Case Report.International medical case reports journal · 2026Article
- AMPD1 and MTHFR genes are not associated with calcium levels in rheumatoid arthritis patients with methotrexate therapy in Indonesia.Scientific reports · 2025Article
- Methotrexate Intolerance in Juvenile Idiopathic Arthritis: Definition, Risks, and Management.Paediatric drugs · 2024Review
- Cross-Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score Questionnaire in Portuguese (Brazil) for Children and Adolescents with Juvenile Idiopathic Arthritis.Journal of clinical medicine · 2023Article
- The impact of single nucleotide polymorphisms inArchives of medical science : AMS · 2023Article
- Pharmacological conditioning for juvenile idiopathic arthritis: a potential solution to reduce methotrexate intolerance.Pediatric rheumatology online journal · 2020Article
- [MTX intolerance in children and adolescents with juvenile idiopathic arthritis].Zeitschrift fur Rheumatologie · 2019Review
- Increased methotrexate intolerance in juvenile idiopathic arthritis compared to acute lymphoblastic leukaemia in children.PloS one · 2019Article
- Successful treatment of methotrexate intolerance in juvenile idiopathic arthritis using eye movement desensitization and reprocessing - treatment protocol and preliminary results.Pediatric rheumatology online journal · 2018Article
- MISS questionnaire in French version: a good tool for children and parents to assess methotrexate intolerance.Clinical rheumatology · 2017Article
- In the Pursuit of Methotrexate Treatment Response Biomarker in Juvenile Idiopathic Arthritis-Are We Getting Closer to Personalised Medicine?Current rheumatology reports · 2017Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethotrexate (MTX) intolerance is a frequent problem of long-term treatment in juvenile idiopathic arthritis (JIA). Mutations in the methylentetrahydrofolate reductase (MTHFR) gene may increase toxicity of MTX, potentially constituting an initial stimulus for this conditioned response. The objective of this study was to investigate the relationship of common MTHFR gene mutations and occurrence of MTX intolerance in pediatric patients with JIA treated with MTX.
methodsConsecutive JIA patients on at least 3 months of MTX treatment were included in this study. Intolerance to MTX was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire, and MTX intolerance was defined as MISS values of ≥ 6. Presence of the two most common mutations in the MTHFR gene (C677T and A1298C) was tested using a PCR assay. Results were analyzed using descriptive and non-parametric statistics.
results196 patients were included (73 % female). Of those, 93 (46 %) showed MTX intolerance. 168 patients were genotyped for C677T and A1298C. MTX intolerance was not found to be significantly more frequent among patients with hetero- and homozygous or homozygous mutations C677T or A1298C compared to wild type or heterozygous mutations. Analysis of the correlation between numbers of mutations in these two loci to the MISS score did not yield a statistically significant correlation.
conclusionMutations in the MTHFR gene were not found to be significantly more frequent in JIA patients intolerant to MTX. Toxicity associated with the MTHFR gene seems to result from mechanisms different to those involved in clinical MTX intolerance.
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