title: Reduced folate carrier 1 gene expression levels are correlated with methotrexate efficacy in Japanese patients with rheumatoid arthritis.
abstract: Responsiveness to methotrexate (MTX), the "anchor drug" for treating rheumatoid arthritis (RA), varies among individual patients. In this study we investigated the effects of folate transporter gene expression levels on disease activity among 56 Japanese patients with RA who were undergoing MTX therapy. We also assessed gene expression levels for 15 healthy control subjects. The mRNA expression levels of reduced folate carrier 1 (RFC1) and proton-coupled folate transporter (PCFT) in PBMCs from these patients and controls were determined using real-time quantitative polymerase chain reaction (PCR). Compared with PCFT, there were large individual differences in RFC1 mRNA expression levels in both RA patients and healthy controls. RFC1 mRNA expression levels and RA disease activity scores were significantly negatively correlated, as disease activity scores were lower for patients with higher RFC1 mRNA expression levels. However, RFC1 mRNA levels were not correlated with MTX doses. Thus, the clinical efficacy of MTX for Japanese RA patients was associated with the expression level of a folate transporter gene. Increased RFC1 expression may increase MTX uptake by immune cells, such as lymphocytes, and as a result, RA disease activity would be reduced.
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Tazoe
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan; Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: hayashih@gifu-pu.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Rheumatology, Shizuoka Kousei Hospital, Aoi-ku, Shizuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsuboi
authors.affiliation: Department of Rheumatology, Shizuoka Kousei Hospital, Aoi-ku, Shizuoka, Japan.
authors.forename: Tomone
authors.initials: T
authors.lastname: Shioura
authors.affiliation: Department of Pharmacy, Shizuoka Kousei Hospital, Aoi-ku, Shizuoka, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: Department of Drug Evaluation and Informatics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan. Electronic address: itohk@u-shizuoka-ken.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000097:blood / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D064368:Healthy Volunteers; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008727:Methotrexate / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D058979:Proton-Coupled Folate Transporter / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents; D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; C120043:SLC19A2 protein, human; C505058:SLC46A1 protein, human; D008727:Methotrexate
keywords: Gene expression level; Genetic polymorphism; Methotrexate; Proton-coupled folate transporter; Reduced folate carrier 1; Rheumatoid arthritis