title: A single nucleotide polymorphism of reduced folate carrier 1 predicts methotrexate efficacy in Japanese patients with rheumatoid arthritis.
abstract: Methotrexate (MTX) exhibits large inter-individual and inter-ethnic differences in the dose required for its anti-rheumatic effect. To maintain low disease activity, patients may require increased MTX doses or co-administration of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The availability of a marker predicting the effect of MTX will make it possible to increase the MTX dose and prescribe bDMARDs to patients at an early stage. To establish individualized medication for rheumatoid arthritis (RA), we investigated genetic polymorphisms of the folate pathway in Japanese RA patients. Eighty-nine patients were treated with MTX alone (MTX group). MTX and bDMARDs were co-administered to 81 patients because of insufficient MTX efficacy (MTX + bDMARDs group); an equally stable therapeutic effect was achieved in both groups. Polymorphism analyses using bDMARD co-treatment as the objective variable revealed a significant association between age and the G80A polymorphism of the reduced folate carrier 1 gene (RFC1) as an explanatory variable. Compared to patients with the A allele, patients with the G allele may have less intracellular MTX uptake and, therefore, poor efficacy; a greater number of them were found to be bDMARD concomitant cases. The results of this study suggest that the RFC1 G80A polymorphism may be a useful marker for predicting MTX efficacy in Japanese patients with RA.
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, and Department of Rheumatology, Shizuoka Kousei Hospital, Shizuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Yui
authors.initials: Y
authors.lastname: Tazoe
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsuboi
authors.forename: Masato
authors.initials: M
authors.lastname: Horino
authors.forename: Mariko
authors.initials: M
authors.lastname: Morishita
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Arai
authors.forename: Motohiro
authors.initials: M
authors.lastname: Ohshima
authors.forename: Taiji
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kosuge
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D054316:Biomarkers, Pharmacological / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D057285:Precision Medicine / Q000379:methods*; D058978:Reduced Folate Carrier Protein / Q000235:genetics*
chemical_list: D018501:Antirheumatic Agents; D054316:Biomarkers, Pharmacological; D058978:Reduced Folate Carrier Protein; D008727:Methotrexate