Development the efficacious pharmacotherapy based on PK/PD/PGx analyses in patients with rheumatoid arthritis

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790164
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: HAYASHI Hideki 静岡県立大学, 薬学部, 講師 (00419665)
• Project Period (FY): 2010 – 2011
• Keywords: 薬学 / 臨床薬理学 / 薬理遺伝学 / 薬剤反応性 / 医療・福祉 / 関節リウマチ / メトトレキサート

Research Abstract

A patient's responsiveness to methotrexate(MTX) for treating rheumatoid arthritis(RA) has the individual differences. The present study examined genetic polymorphisms related to folate metabolism pathway and concentrations of MTX and its active form, MTX. polyglutamates(MTX. PGs), in red blood cells(RBCs) in RA patients. The patients with the G allele of the G80A polymorphism of the folate transporter gene RFC1 had less intracellular MTX uptake and therefore had poor efficacy ; a greater number of them were found to be biological preparations concomitant cases. The results of the present study suggest the possibility that the RFC1 G80A polymorphism and MTX. PGs levels in patients' RBCs may be a useful marker for predicting MTX efficacy in Japanese patients with RA.

Research Products

• [Journal Article] An artifact derived from a pseudogene led to the discovery of microRNA binding site polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene (2012)
  • Author(s): Hayashi H, Tazoe Y, Horino M, Fujimaki-Katoh C, Tsuboi S, Matsuyama T, Kosuge K, Yamada H, Tsuji D, Inoue K, Itoh K
  • Journal Title: Drug Metab. Pharmacokinet Volume: 27 Pages: 263-267
• [Journal Article] 薬効モニタリングの実践-16 (2011)
  • Author(s): 林秀樹, 伊藤邦彦
  • Journal Title: 関節リウマチ Volume: 62 Pages: 126-131
• [Journal Article] Dihydrofolate reductase gene intronic 19-bp deletion polymorphisms in a Japanese population (2010)
  • Author(s): Hayashi H, Horino M, Morishita M, Tazoe Y, Tsuboi S, Matsuyama T, Kosuge K, Yamada H, Tsuji D, Inoue K, Itoh K
  • Journal Title: Drug Metab. Pharmacokinet Volume: 25 Pages: 516-518
• [Presentation] 抗リウマチ薬メトトレキサートの赤血球中濃度と遺伝子多型の関連性の検討 (2012)
  • Author(s): 田添唯, 林秀樹, 森下茉莉子, 坪井声示, 松山耐至, 荒井輝久, 大鹿雄美, 小菅和仁, 山田浩, 辻大樹, 井上和幸, 伊藤邦彦
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] 抗リウマチ薬メトトレキサートの効果不十分症例における遺伝的因子の解析 (2011)
  • Author(s): 田添唯、林秀樹、森下茉莉子、坪井声示、松山耐至、荒井輝久、大鹿雄美、小菅和仁、山田浩、辻大樹、井上和幸、伊藤邦彦
  • Organizer: 第32回日本臨床薬理学会年会
  • Place of Presentation: 浜松
  • Year and Date: 2011-12-01
• [Presentation] ジヒドロ葉酸還元酵素の遺伝子多型がメトトレキサートの抗リウマチ効果に及ぼす影響の検討 (2011)
  • Author(s): 田添唯、堀野雅人、林秀樹、森下茉莉子、坪井声示、松山耐至、小菅和仁、山田浩、辻大樹、井上和幸、伊藤邦彦
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-29