ArticlePloS one2014
Role of key TYMS polymorphisms on methotrexate therapeutic outcome in portuguese rheumatoid arthritis patients.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 5 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 5 syntheses or guidelines pooled it, 43 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
- 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
- The genetic puzzle of rheumatoid arthritis: Causes, progression, and treatment.Biochemistry and biophysics reports · 2025Review
- The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.Clinical rheumatology · 2024Article
- Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota.The pharmacogenomics journal · 2022Article
- Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer.Frontiers in immunology · 2022Article
- Article
- 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
- A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology.Journal of ophthalmology · 2020Review
- Oxyphenbutazone promotes cytotoxicity in rats and Hep3B cellsvia suppression of PGEMolecular and cellular biochemistry · 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
- Clinical Pharmacogenetic Models of Treatment Response to Methotrexate Monotherapy in Slovenian and Serbian Rheumatoid Arthritis Patients: Differences in Patient's Management May Preclude Generalization of the Models.Frontiers in pharmacology · 2018Article
- Clinical-pharmacogenetic predictive models for MTX discontinuation due to adverse events in rheumatoid arthritis.The pharmacogenomics journal · 2017Article
- Effect of thymidylate synthase (TYMS) gene polymorphisms with methotrexate treatment outcome in south Indian Tamil patients with rheumatoid arthritis.Clinical rheumatology · 2017Article
- Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway.European journal of drug metabolism and pharmacokinetics · 2016Article
- Impaired NFKBIE gene function decreases cellular uptake of methotrexate by down-regulating SLC19A1 expression in a human rheumatoid arthritis cell line.Modern rheumatology · 2016Article
- Preliminary study for predicting better methotrexate efficacy in Japanese patients with rheumatoid arthritis.Journal of pharmaceutical health care and sciences · 2016Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTherapeutic outcome of rheumatoid arthritis (RA) patients treated with methotrexate (MTX) can be modulated by thymidylate synthase (TS) levels, which may be altered by genetic polymorphisms in TS gene (TYMS). This study aims to elucidate the influence of TYMS polymorphisms in MTX therapeutic outcome (regarding both clinical response and toxicity) in Portuguese RA patients.
methodsClinicopathological data from 233 Caucasian RA patients treated with MTX were collected, outcomes were defined and patients were genotyped for the following TYMS polymorphisms: 1) 28 base pairs (bp) variable number tandem repeat (rs34743033); 2) single nucleotide polymorphism C>G (rs2853542); and 3) 6 bp sequence deletion (1494del6, rs34489327). Chi-square and binary logistic regression analyses were performed, using genotype and haplotype-based approaches.
resultsConsidering TYMS genotypes, 3R3R (p = 0.005, OR = 2.34), 3RC3RG (p = 0.016, OR = 3.52) and 6bp- carriers (p = 0.011, OR = 1.96) were associated with non-response to MTX. Multivariate analysis confirmed the increased risk for non-response to MTX in 6bp- carriers (p = 0.016, OR = 2.74). Data demonstrated that TYMS polymorphisms were in linkage disequilibrium (p<0.00001). Haplotype multivariate analysis revealed that haplotypes harboring both 3R and 6bp- alleles were associated with non-response to MTX. Regarding MTX-related toxicity, no statistically significant differences were observed in relation to TYMS genotypes and haplotypes.
conclusionOur study reveals that TYMS polymorphisms could be important to help predicting clinical response to MTX in RA patients. Despite the potential of these findings, translation into clinical practice needs larger studies to confirm these evidences.
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