ArticleEuropean journal of drug metabolism and pharmacokinetics2016
Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway.
Article in European journal of drug metabolism and pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 4 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 4 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- The impact of gene polymorphisms on the response of methotrexate-based treatments.European journal of clinical pharmacology · 2026Pooled it
- Genetic markers in methotrexate treatments.The pharmacogenomics journal · 2018Pooled it
- TYMS polymorphisms and responsiveness to or toxicity of methotrexate in rheumatoid arthritis.Zeitschrift fur Rheumatologie · 2018Pooled it
- Pooled it
- The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.Clinical rheumatology · 2024Article
- MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis.Pharmacogenomics and personalized medicine · 2023Article
- Capturing the Catalytic Proton of Dihydrofolate Reductase: Implications for General Acid-Base Catalysis.ACS catalysis · 2021Article
- 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
- Wasp Venom Possesses Potential Therapeutic Effect in Experimental Models of Rheumatoid Arthritis.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian Tamil Rheumatoid Arthritis patients.Clinical and experimental medicine · 2018Article
- Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population.Frontiers in pharmacology · 2018Article
- Article
- MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate.Genetic testing and molecular biomarkers · 2017Article
- Effect of thymidylate synthase (TYMS) gene polymorphisms with methotrexate treatment outcome in south Indian Tamil patients with rheumatoid arthritis.Clinical rheumatology · 2017Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveMethotrexate (MTX) is a disease-modifying anti-rheumatic drug used in the treatment of rheumatoid arthritis (RA). It is the first line drug in the treatment of this disease. However, MTX-related adverse drug reactions (ADRs) are seen in 40 % of the patients. The aim of this study was to determine the impact of six genetic polymorphisms located in five genes encoding proteins involved in the MTX metabolic pathway in Tunisian RA patients and evaluate its association with MTX toxicity.
methodsGenotyping of 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), dihydrofolate reductase (DHFR 19-base pair deletion allele), thymidylate synthase (TYMS 2R/3R), methionine synthase (MTR A2756G) and methionine synthase reductase (MTRR A66G) was performed using PCR and PCR-RFLP method in 141 RA patients treated with MTX. Demographic and clinical characteristics were obtained and ADRs were recorded. Association analyses with regard to MTX toxicity were performed using the χ (2) test, the toxicogenetic risk index (TRI) and the Mann-Whitney U-test.
resultsThe analysis highlighted a significant association of the T/T genotype of MTHFR C677T polymorphism with increased MTX toxicity. However, the MTHFR A1298C, DHFR 19-base pair deletion allele, MTR A2756G and MTRR A66G polymorphisms were not associated with increased MTX toxicity. The TYMS 2R/3R polymorphism had a protective effect against MTX toxicity.
conclusionThe results demonstrated that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in Tunisian RA patients. In contrast, the TYMS 2R/3R polymorphism is associated with a protective effect against overall MTX toxicity.
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