ArticleRheumatology international2015
The impact of C677T and A1298C MTHFR polymorphisms on methotrexate therapeutic response in East Bohemian region rheumatoid arthritis patients.
Article in Rheumatology international, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 5 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 5 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Dutch pharmacogenetics working group guideline for the gene-drug interaction of ABCG2, HLA-B and Allopurinol, and MTHFR, folic acid and methotrexate.European journal of human genetics : EJHG · 2024Guideline
- Predictive genetic biomarkers for the efficacy of methotrexate in rheumatoid arthritis: a systematic review.The pharmacogenomics journal · 2020Pooled 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
- MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis.Pharmacogenomics and personalized medicine · 2023Article
- Higher Risk of Cardiovascular Diseases in Rheumatoid Arthritis Patients Without Methotrexate Treatment.Frontiers in pharmacology · 2021Article
- Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response.International journal of molecular sciences · 2020Review
- 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
- Methotrexate impact on radiographic progression in biologic-treated rheumatoid arthritis under clinical remission: A case report on monozygotic Caucasian twins.International journal of immunopathology and pharmacology · 2016Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Some single-nucleotide polymorphisms (SNPs) might be predictive of methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA). The aim of this study was to determine whether SNPs in the methylenetetrahydrofolate reductase (MTHFR) gene are predictive of MTX response. Comparison was made using EULAR response criteria and according to the change of DAS28 (∆DAS28) after a 6-month MTX treatment in RA patient cohort. The two SNPs C677T (rs1801133) and A1298C (rs1801131) have been genotyped. A total of 120 patients were enrolled in the study, and all of them fulfilled the American College of Rheumatology 1987 RA criteria and are currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with other disease-modifying antirheumatic drugs (n = 55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T and A1298C genotypes with MTX treatment inefficacy in dominant model (OR 1.23, 95 % CI 0.57-2.65, P = 0.697; and OR 0.98, 95 % CI 0.47-2.14, P = 1.0, respectively), or in recessive and codominant models. However, when ∆DAS28 after a 6-month therapy was used as a measure of treatment efficacy, the 677CT and 1298AC genotypes were found to be significantly associated with less favorable response to MTX (P = 0.025 and P = 0.043, respectively). In addition, even lower ∆DAS28 was determined for double-mutated 677CT-1298AC heterozygotes. It means that a synergistic effect of 677CT and 1298AC genotypes was observed. Nevertheless, the DAS28 baseline was lower here comparing to other genotypes. Unexpectedly, quite the opposite trend-i.e., better response to MTX-was found in genotypes 677CC-1298CC and 677TT-1298AA. It is an intriguing finding, because these double-mutated homozygotes are known for their low MTHFR-specific activity. Global significance was P = 0.013, η (2) = 0.160-i.e., large-size effect. Thus, our data show greater ability of 677CC-1298CC and 677TT-1298AA genotypes to respond to MTX treatment.
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