Functional characterization of drug metabolizing enzyme genes and variant proteins

• Project/Area Number: 20590154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: HIRATSUKA Masahiro Tohoku University, 大学院・薬学研究科, 准教授 (50282140)
• Co-Investigator(Kenkyū-buntansha): 佐々木 崇光 東北薬科大学, 薬学部, 助手 (20382674)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ゲノム / 酵素 / 薬剤反応性 / 遺伝子 / 蛋白質

Research Abstract

Drug metabolizing enzymes, CYP2D6, CYP2B6, and TPMT are enzymes of potential importance for the metabolism of clinically used drugs, and it exhibits genetic polymorphism with interindividual differences in metabolic activity. The aim of this study was to investigate the functional characterization of CYP2D6, CYP2B6, and TPMT variants. Functional characterization of 17 CYP2D6, 26 CYP2B6, and 23 TPMT variants revealed an altered enzyme activity of a number of allelic variants.

Research Products

• [Journal Article] Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene. (2010)
  • Author(s): Mutsumi Kudo, Takamitsu Sasaki, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka.
  • Journal Title: Drug Metab. Pharmacokinet. 25 Pages: 599-604
  • NAID: 10027743970
  • Peer Reviewed
• [Journal Article] Kinetics of 6-thioxanthine metabolism by allelic variants of xanthine oxidase. (2010)
  • Author(s): Mutsumi Kudo, Takamitsu Sasaki, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka.
  • Journal Title: Drug Metab. Pharmacokinet. 25 Pages: 361-366
  • NAID: 10027583274
  • Peer Reviewed
• [Journal Article] Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2?CYP2B6.28, except CYP2B6.22). (2010)
  • Author(s): Takashi Watanabe, Kanako Sakuyama, Takamitsu Sasaki, Yuya Ishii, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka.
  • Journal Title: Pharmacogenet. Genom. 20 Pages: 459-462
  • Peer Reviewed
• [Journal Article] Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2-CYP2B6.28, except CYP2B6.22) (2010)
  • Author(s): 渡辺卓嗣、平塚真弘, ら
  • Journal Title: Pharmacogenet.Genom. Volume: 20 Pages: 459-462
  • Peer Reviewed
• [Journal Article] Kinetics of 6-thioxanthine metabolism by allelic variants of xanthine oxidase (2010)
  • Author(s): 工藤睦、平塚真弘, ら
  • Journal Title: Drug Metab.Pharmacokinet. Volume: 25 Pages: 361-366
  • NAID: 10027583274
  • Peer Reviewed
• [Journal Article] Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene (2010)
  • Author(s): 工藤睦、平塚真弘, ら
  • Journal Title: Drug Metab.Pharmacokinet. Volume: 25 Pages: 599-604
  • NAID: 10027743970
  • Peer Reviewed
• [Journal Article] Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals. (2009)
  • Author(s): Mutsumi Kudo, Yuka Saito, Takamitsu Sasaki, Hitomi Akasaki, Yuri Yamaguchi, Moe Uehara, Kiyomi Fujikawa, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka.
  • Journal Title: Drug Metab. Pharmacokinet. 24 Pages: 557-564
  • NAID: 10027119756
  • Peer Reviewed
• [Journal Article] Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals (2009)
  • Author(s): 工藤睦、平塚真弘, ら
  • Journal Title: Drug Metabolism and Pharmacokinetics 24 Pages: 557-564
  • NAID: 10027119756
  • Peer Reviewed
• [Journal Article] Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57). (2008)
  • Author(s): Kanako Sakuyama, Takamitsu Sasaki, Shuta Ujiie, Kanako Obata, Michinao Mizugaki, Masaaki Ishikawa, Masahiro Hiratsuka.
  • Journal Title: Drug Metab. Dispos. 36 Pages: 2460-2467
  • Peer Reviewed
• [Journal Article] Functional characterization of 23 allelic variants of thiopurine S-methyltransferase gene (TPMT*2-*24). (2008)
  • Author(s): Shuta Ujiie, Takamitsu Sasaki, Michinao Mizugaki, Masaaki Ishikawa, Masahiro Hiratsuka.
  • Journal Title: Pharmacogenet. Genom. 18 Pages: 887-893
  • NAID: 130005024445
  • Peer Reviewed
• [Journal Article] Functional characterization of 23 allelic variants of t hiopurine S-methyltransferase gene (TPMT*2-*24) (2008)
  • Author(s): 氏家秀太、平塚真弘, ら
  • Journal Title: Pharmacogenetics and genomics 18 Pages: 887-893
  • NAID: 130005024445
  • Peer Reviewed
• [Journal Article] Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57) (2008)
  • Author(s): 作山佳奈子、平塚真弘, ら
  • Journal Title: Drug Metabolism and Disposition 36 Pages: 2460-2467
  • Peer Reviewed
• [Presentation] 薬物代謝酵素遺伝子のSNP スクリーニングとバリアント酵素の機能変化解析に関する研究 (2010)
  • Author(s): 平塚真弘
  • Organizer: 日本薬物動態学会
  • Place of Presentation: 埼玉
  • Year and Date: 2010-10-08
• [Presentation] 薬物代謝酵素遺伝子のSNPスクリーニングとバリアント酵素の機能変化解析に関する研究 (2010)
  • Author(s): 平塚真弘
  • Organizer: 日本薬物動態学会
  • Place of Presentation: 埼玉
  • Year and Date: 2010-10-08
• [Presentation] 薬剤管理指導におけるファーマコゲノミクス情報の利用 (2009)
  • Author(s): 平塚真弘
  • Organizer: 第36回日本医療薬学会公開シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2009-11-14
• [Presentation] Functional Characterization of Xanthine Oxidase Allelic Variants (2009)
  • Author(s): 平塚真弘
  • Organizer: 13th International Symposium on Purine and Pyrimidine Metabolism in Man
  • Place of Presentation: ストックホルム、スウェーデン
  • Year and Date: 2009-06-24
• [Presentation] 日本人におけるCYP2D6バリアント酵素の機能解析 (2008)
  • Author(s): 作山佳奈子、平塚真弘
  • Organizer: 日本臨床薬理学会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-05
• [Presentation] 日本人におけるCYP2D6バリアント酵素の機能解析 (2008)
  • Author(s): 作山佳奈子
  • Organizer: 第29回日本臨床薬理学会年会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-05
• [Presentation] チオプリンS-メチルトランスフェラーゼの23種バリアント酵素の機能解析 (2008)
  • Author(s): 平塚真弘
  • Organizer: 日本薬物動態学会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-31
• [Presentation] CYP2B6遺伝子多型によるバリアント酵素の機能解析 (2008)
  • Author(s): 渡邊卓嗣、平塚真弘
  • Organizer: 日本薬物動態学会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-31
• [Presentation] CYP2B6遺伝子多型によるバリアント酵素の機能解析 (2008)
  • Author(s): 渡邊卓嗣
  • Organizer: 日本薬物動態学会第23回年会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-31
• [Presentation] チオプリンS-メチルトランスフェラーゼの23種バリアント酵素の機能解析 (2008)
  • Author(s): 平塚真弘
  • Organizer: 日本薬物動態学会第23回年会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-31
• [Book] 遺伝子診療学(第2版)-遺伝子診断の進歩とゲノム治療の展望(日本臨牀) (2010)
  • Author(s): 平塚真弘、工藤睦、作山佳奈子
• [Book] 遺伝子診療学(第2版)-遺伝子診断の進歩とゲノム治療の展望 (2010)
  • Author(s): 平塚真弘、工藤睦、作山佳奈子
  • Publisher: 日本臨牀