Development of the strategic pharmacotherapy using the genetic polymorphisms and the pharmacokinetics in the rheumatoid arthritis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Gifu Pharmaceutical University (2014-2015); University of Shizuoka (2013)
• Principal Investigator: Hayashi Hideki 岐阜薬科大学, 薬学部, 准教授 (00419665)
• Co-Investigator(Kenkyū-buntansha): TODOROKI Kenichiro 静岡県立大学, 薬学部, 准教授 (70341451) ; YAMADA Hiroshi 静岡県立大学, 薬学部, 教授 (40265252) ; ITOH Kunihiko 静岡県立大学, 薬学部, 教授 (90221770)
• Research Collaborator: TAZOE Yui 静岡県立大学, 大学院, 大学院生 ; TSUBOI Seiji JA静岡厚生病院, 副院長 ; MATSUYAMA Taiji JA静岡厚生病院, 薬局長
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 関節リウマチ / メトトレキサート / 個別化医療 / 遺伝子解析 / 葉酸トランスポーター / TDM

Outline of Final Research Achievements

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 in the Japanese patients with RA who were undergoing MTX therapy. The mRNA expression levels of reduced folate carrier 1 (RFC1) in PBMCs from these patients were determined. There were large individual differences in RFC1 mRNA expression levels in both RA patients. 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. Thus, the clinical efficacy of MTX for Japanese RA patients was associated with the expression level of a folate transporter gene. We also attempted the therapeutic drug monitoring using measurement of the biological preparation in plasma and methotrexate and its active metabolite in red blood cells.

Free Research Field

臨床薬理学