ArticleJournal of pharmaceutical health care and sciences2016
Genetic polymorphisms of enzyme proteins and transporters related to methotrexate response and pharmacokinetics in a Japanese population.
Article in Journal of pharmaceutical health care and sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- MTHFR gene polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis based on 16 studies.Clinical rheumatology · 2020Pooled it
- Factors Underlying Failure of Methotrexate Treatment in Rheumatoid Arthritis: Implications in Personalized Care.Archives of internal medicine research · 2025Article
- Pharmacogenetic Basis of Response Fluctuations to Methotrexate in Rheumatoid Arthritis: A Narrative Review.Current rheumatology reviews · 2025Review
- Impact of microRNA polymorphisms on high-dose methotrexate-related hematological toxicities in pediatric acute lymphoblastic leukemia.Frontiers in pediatrics · 2023Article
- Can we predict unresponsiveness to methotrexate in rheumatoid arthritis? A pharmacogenetic study.Inflammopharmacology · 2022Article
- Dermatology: how to manage psoriasis and recognize differences in pathophysiology and presentation in patients with skin of colour.Drugs in context · 2022Review
- Enzymes involved in folate metabolism and its implication for cancer treatment.Nutrition research and practice · 2020Review
- Association ofThe Journal of international medical research · 2020Article
- Do SNPs in folate pharmacokinetic pathway alter levels of intracellular methotrexate polyglutamates and affect response? A prospective study in Indian patients.Clinical rheumatology · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethotrexate (MTX) is currently the anchor drug widely used worldwide in the treatment of rheumatoid arthritis (RA). However, the therapeutic response to MTX has been shown to vary widely among individuals, genders and ethnic groups. The reason for this has been not clarified but it is considered to be partially due to several mechanisms in the cellular pathway of MTX including single-nucleotide polymorphisms (SNPs). The purpose of this study was to investigate the allelic frequencies in different ethnic and/or population groups in the 10 polymorphisms of enzyme proteins and transporters related to the MTX response and pharmacokinetics including MTHFR, TYMS, RFC1, FPGS, GGH, ABCB1, ABCC2 and ABCG2 in unrelated healthy Japanese adults and patients with RA.
methodsTen polymorphisms, methylenetetrahydrofolate reductase (MTHFR) 1298, thymidylate synthase (TYMS) 3'-UTR, reduced folate carrier 1 (RFC1) 80 and-43, folypolyglutamyl synthase (FPGS) 1994, γ-glutamyl hydrolase (GGH) 452 and-401, the ABC transporters (ABCB1 3435, ABCC2 IVS23 + 56, ABCG2 914) of enzyme proteins and transporters related to MTX response and pharmacokinetics in 299 unrelated healthy Japanese adults and 159 Japanese patients with RA were investigated to clarify their contributions to individual variations in response and safety to MTX and establish personalized MTX therapy. SNPs were evaluated using real-time polymerase chain reaction (PCR).
resultsComparison of allelic frequencies in our study with other ethnic/population groups of healthy adults and RA patients showed significant differences in 10 polymorphisms among healthy adults and 7 among RA patients. Allelic frequencies of MTHFR 1298 C, FPGS 1994A and ABCB1 3435 T were lower in Japanese than in Caucasian populations and those of ABCC2 IVS23 + 56 C and ABCG2 914A were higher in Japanese than in Caucasian/European populations in both healthy adults and RA patients. Allelic frequencies of MTHFR 1298 C, GGH-401 T, ABCB1 3435 T, and ABCG2 914A were higher in healthy Japanese adults than in an African population, and those of RFC1 80A, RFC1-43C and ABCC2 IVS23 + 56 C in healthy Japanese adults were lower than in Africans. However, no significant differences were seen in the distribution of allelic frequencies between healthy Japanese adults and RA patients.
conclusionThe variations in allelic frequencies in different ethnic and/or population groups in healthy adults and RA patients may contribute to individual variations in MTX response and toxicity.
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