ArticleClinical rheumatology2024
The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.
Article in Clinical rheumatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 2 citations in OpenAlex.
- The impact of gene polymorphisms on the response of methotrexate-based treatments.European journal of clinical pharmacology · 2026Pooled it
- Diagnostic, prognostic and therapeutic biomarkers in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Multi-cohort Analysis Reveals Microbiome Signatures Associated with Drug Response in New-Onset Rheumatoid Arthritis.bioRxiv : the preprint server for biology · 2026Article
- The association between methotrexate metabolism-related gene polymorphisms and therapeutic efficacy and toxicity in patients with rheumatoid arthritis.Arthritis research & therapy · 2026Article
- Review
- Recent Advances on the Role of B Vitamins in Cancer Prevention and Progression.International journal of molecular sciences · 2025Review
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere are currently no validated criteria that entirely explain or predict response to methotrexate (MTX) treatment in rheumatoid arthritis (RA). We tried to identify the connection between three variants (RFC1 G80A (rs1051266), TYMS 2R/3R (rs34743033), and ATIC C347G (rs2372536)) in the folate pathway of MTX metabolism and the response to MTX monotherapy in a cohort of RA cases.
methodsA prospective study on 100 RA patients on MTX monotherapy was performed. Disease activity was measured at the start of treatment and 6 months after treatment with MTX. The patients were then split into two groups: those who responded to the treatment and those who did not. The molecular genetic study for the RFC1 (G80A) variant was employed via the PCR-restriction fragment length polymorphism (PCR-RFLP) technique, the ATIC (C347G) variant was performed using TaqMan allelic discrimination real-time PCR, and the tandem repeat sequences of TYMS (2R/3R) were amplified by conventional PCR and detected by agarose gel electrophoresis.
resultsThe genotype distribution of RFC-1 (G80A) showed significant variations among non-responders and responders in the recessive genetic model. A significant difference was found in TYMS (2R/3R) in the dominant and heterozygous genetic models. However, ATIC (C347G) genotype frequency did not exhibit substantial link with drug response in all genetic models. Furthermore, the genotype and allele rates of the analyzed variants did not show any significant association with adverse events in all genetic models.
conclusionThe 80AA genotype of RFC-1 G80A and the 2R/3R or 3R/3R genotypes of TYMS 2R/3R are more vulnerable to the good consequences of MTX therapy. Key Points • Current recommendations support the gold standard role of MTX as a first-line monotherapy for RA patients. However, up to 40% of RA patients do not respond or exhibit partial response to MTX. • Persistent disease activity due to treatment unresponsiveness will affect the long-term outcomes in RA patients. • We aimed, through molecular genetic study, to identify the connection between three variants in the folate pathway of MTX metabolism and the response to methotrexate monotherapy in a cohort of RA patients.
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