Association of genotypes for drug-binding protein with anti-cancer drug responses

• Project/Area Number: 21590191
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: National Institute of Health Sciences
• Principal Investigator: SAI Kimie 国立医薬品食品衛生研究所, 医薬安全科学部, 室長 (20195960)
• Co-Investigator(Kenkyū-buntansha): KATORI Noriko 国立医薬品食品衛生研究所, 薬品部, 室長 (60142121) ; KUROSE Koichi 国立医薬品食品衛生研究所, 医薬安全科学部, 室長 (30280754) ; SAITO Yoshiro 国立医薬品食品衛生研究所, 医薬安全科学部, 部長 (50215571)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: オーダーメード医療 / α-1-酸性糖蛋白 / 薬剤反応性 / 遺伝子多型 / ハプロタイプ / ゲノム / 臨床 / 薬理学 / 抗がん剤 / 遺伝子

Research Abstract

This study was aimed to identify genetic polymorphisms of ORM genes(ORM1 and ORM2), encodingα-1-acid glycoprotein(AGP), which might affect anti-cancer drug responses. Detailed analysis on ORM gene structures(duplication/deletion) and genetic polymorphisms/haplotypes were conducted for Japanese cancer patients who received paclitaxel(PTX)-therapy, and the association of ORM genotypes with serum AGP levels and PTX-pharmacokinetics were investigated. As a result, ORM genetic polymorphisms related to increased levels of serum AGP and the area under the plasma concentration-time curves of PTX-metabolites were identified. A luciferase reporter gene assay indicated existence of putative promoter regions which might be responsible for different regulatory mechanisms of gene expression between ORM1 and ORM2.Possible influence of the ORM genetic polymorphism on the reporter activity was also examined.

Research Products

• [Journal Article] Genetic variations of orosomucoid genes associated with serum alpha-1-acid glycoprotein level and the pharmacokinetics of paclitaxel in Japanese cancer patients (2011)
  • Author(s): Katori N, Sai K, Saito Y, Fukushima-Uesaka H, Kurose K,(fifteen other co-authors)
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 100 Pages: 4546-4559
  • Peer Reviewed
• [Presentation] パクリタキセル投与患者におけるα1-acid glycoproteinと遺伝子多型、薬物動態および患者背景因子の関連性 (2011)
  • Author(s): 香取典子、佐井君江、斎藤嘉朗, 他14名
  • Organizer: 日本薬学会第131年回
  • Place of Presentation: ツインメッセ静岡(静岡)
  • Year and Date: 2011-03-29
• [Presentation] パクリタキセル投与患者におけるα-1-acid glycoproteinと遺伝子多型、薬物動態および患者背景因子の関連性 (2011)
  • Author(s): 香取典子、佐井君江、斎藤嘉朗、福島(上坂)浩美、黒瀬光一(他12名)
  • Organizer: 日本薬学会第131年回
  • Place of Presentation: ツインメッセ静岡(静岡)
• [Presentation] 日本人癌患者のORM遺伝子多型による血中α1酸性糖蛋白レベルへの影響 (2010)
  • Author(s): 香取典子、佐井君江、斎藤嘉朗, 他14名
  • Organizer: 第25回日本薬物動態学会年会
  • Place of Presentation: 大宮ソニックシティ(埼玉)
  • Year and Date: 2010-10-07
• [Presentation] 日本人癌患者のORM遺伝子多型による血中α-1-酸性糖蛋白レベルへの影響 (2010)
  • Author(s): 香取典子、佐井君江、斎藤嘉朗、福島(上坂)浩美、黒瀬光一、(他12名)
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉)
• [Presentation] Haplotype structure of genes encoding α1-acid glycoprotein in a Japanese population (2009)
  • Author(s): 香取典子、斎藤嘉朗、佐井君江, (他15名)
  • Organizer: 第24回日本薬物動態学会年会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2009-11-27
• [Presentation] Genetic polymorphisms of ORM1 and ORM2 genes encoding al-acid glycoproteins in a Japanese population (2009)
  • Author(s): 香取典子、斎藤嘉朗、佐井君江, (他15名)
  • Organizer: 第16回ISSX北米大会
  • Place of Presentation: ボルチモア マリオット(ボルチモア、米国)
  • Year and Date: 2009-10-21