ArticleBritish journal of clinical pharmacology2011
Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis.
Article in British journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03006991 (Individual Study of Methotrexate Based on Pharmacogenomics and Pharmacometrics), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
Individual Study of Methotrexate Based on Pharmacogenomics and Pharmacometrics
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review.Pediatric rheumatology online journal · 2014Pooled it
- Impact of Pharmacogenetics on High-Dose Methotrexate Toxicity in Pediatric Oncology.Pharmaceutics · 2025Article
- The role of liver transaminase levels in methotrexate intolerance in juvenile idiopathic arthritis-a cross-sectional study.Rheumatology international · 2023Article
- Genetic variations in methotrexate metabolic pathway genes influence methotrexate responses in rheumatoid arthritis patients in Malaysia.Scientific reports · 2022Article
- Article
- Characterization of pharmacogenetic markers related to Acute Lymphoblastic Leukemia toxicity in Amazonian native Americans population.Scientific reports · 2020Observational
- Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis.Clinical rheumatology · 2020Article
- Early and Accurate Prediction of Clinical Response to Methotrexate Treatment in Juvenile Idiopathic Arthritis Using Machine Learning.Frontiers in pharmacology · 2019Article
- Race, Income, and Disease Outcomes in Juvenile Dermatomyositis.The Journal of pediatrics · 2017Article
- In the Pursuit of Methotrexate Treatment Response Biomarker in Juvenile Idiopathic Arthritis-Are We Getting Closer to Personalised Medicine?Current rheumatology reports · 2017Review
- 5-Aminoimidazole-4-carboxamide ribonucleotide-transformylase and inosine-triphosphate-pyrophosphatase genes variants predict remission rate during methotrexate therapy in patients with juvenile idiopathic arthritis.Rheumatology international · 2015Article
- γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.Genes & nutrition · 2015Article
- Pharmacogenetics: can genes determine treatment efficacy and safety in JIA?Nature reviews. Rheumatology · 2014Review
- Clinically relevant pharmacogenomic testing in pediatric practice.Clinical pediatrics · 2014Article
- Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.International journal of hematology · 2013Article
- γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate.British journal of cancer · 2013Article
- The genetic architecture of methotrexate toxicity is similar in Drosophila melanogaster and humans.G3 (Bethesda, Md.) · 2013Article
- Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients.European journal of clinical pharmacology · 2013Article
- Relating human genetic variation to variation in drug responses.Trends in genetics : TIG · 2012Review
- Genetic variation in folylpolyglutamate synthase and gamma-glutamyl hydrolase and plasma homocysteine levels in the Singapore Chinese Health Study.Molecular genetics and metabolism · 2012Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsWe investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular-type juvenile idiopathic arthritis (JIA).
methodsEight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ-glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non-responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics.
resultsThe non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P=0.028, odds ratio=6.90, 95% confidence interval 1.38-34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P=0.029) and rheumatoid factor positivity (P=0.026, odds ratio=2.87, 95% confidence interval 1.11-7.39) were associated with lower efficacy of MTX.
conclusionsThe non-TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients.
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