Establishment of tailor-made drug therapy that aims at improvement of quality of life in patients with rheumatoid arthritis

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790140
• 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 University of Shizuoka, 薬学部, 講師 (00419665)
• Project Period (FY): 2008 – 2009
• Keywords: 関節リウマチ / メトトレキサート / オーダーメード医療 / 遺伝薬理学 / TDM

Research Abstract

We evaluated the association of possible factors with the cumulative value of C-reactive protein in Japanese patients with RA. Polymorphisms of the reduced folate carrier gene (RFC) G80A and of the gamma-glutamylhydrolase gene (GGH) C-401T were more closely associated (beta = 2.1194, P = 0.0017) than other polymorphisms, with the anti-inflammatory response to MTX. Plasma homocysteine levels in patients with the MTHFR 677TT genotype were significantly higher than in those with the 677CC genotype (p < 0.05). In addition, plasma homocysteine levels were increased along with the elevation of general inflammatory markers.

Research Products

• [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. (in press)
• [Journal Article] Genetic polymorphisms in folate pathway enzymes as a possible marker for predicting the outcome of methotrexate therapy in Japanese patients with rheumatoid arthritis. (2009)
  • Author(s): Hayashi H, Fujimaki C, Daimon T, Tsuboi S, Matsuyama T, Itoh K
  • Journal Title: J. Clin. Pharm. Ther. 34 Pages: 355-361
• [Journal Article] Plasma total homocysteine level and methylenetetrahydrofolate reductase 677C>T genetic polymorphism in Japanese patients with rheumatoid arthritis (2009)
  • Author(s): Fujimaki C, Hayashi H, Tsuboi S, Matsuyama T, Kosuge K, Yamada H, Inoue K, Itoh K
  • Journal Title: Biomarkers 14 Pages: 49-54
• [Presentation] 関節リウマチにおけるmethotrexate反応性予測因子としてのdihydrofolate reductase遺伝子多型 (2010)
  • Author(s): 堀野雅人, 林秀樹, 藤巻千裕, 森下茉莉子, 小菅和仁, 坪井声示, 松山耐至, 山田浩, 井上和幸, 辻大樹, 伊藤邦彦
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 20100000
• [Presentation] 関節リウマチ患者におけるテーラーメイド薬物療法の実現を目指した遺伝子多型解析研究 (2009)
  • Author(s): 藤巻千裕, 林秀樹, 松山耐至, 坪井声示, 井上和幸, 伊藤邦彦
  • Organizer: 第23回静岡県病院薬剤師会学術大会
  • Place of Presentation: 静岡
  • Year and Date: 20090000
• [Presentation] 関節リウマチ患者における赤血球中メトトレキサート活性体濃度測定 (2009)
  • Author(s): 林秀樹, 藤巻千裕, 松山耐至, 坪井声示, 井上和幸, 伊藤邦彦
  • Organizer: 第23回静岡県病院薬剤師会学術大会
  • Place of Presentation: 静岡
  • Year and Date: 20090000
• [Presentation] 関節リウマチ患者におけるメトトレキサートの薬効に影響する遺伝的因子 (2008)
  • Author(s): 林秀樹, 藤巻千裕, 坪井声示, 大門貴志, 松山耐至, 井上和幸, 伊藤邦彦
  • Organizer: 第18回日本医療薬学会年会
  • Place of Presentation: 札幌
  • Year and Date: 20080000
• [Presentation] 関節リウマチ患者における血球中メトトレキサート濃度測定 (2008)
  • Author(s): 林秀樹, 藤巻千裕, 坪井声示, 松山耐至, 井上和幸, 伊藤邦彦
  • Organizer: 第54回日本薬学会東海支部総会・大会
  • Place of Presentation: 名古屋
  • Year and Date: 20080000
• [Presentation] ホモシステインと疾患活動性～関節リウマチにおける検討～ハイライト集収載 (2008)
  • Author(s): 林秀樹, 藤巻千裕, 坪井声示, 松山耐至, 原田直人, 伊藤邦彦
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 20080000