Investigation of clinical impacts of CNV in the pharmacokinetic-related genes

• Project/Area Number: 20390048
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kyushu University
• Principal Investigator: IEIRI Ichiro Kyushu University, 大学院・薬学研究院, 教授 (60253473)
• Co-Investigator(Kenkyū-buntansha): HIROTA Takeshi 九州大学, 大学院・薬学研究院, 助教 (80423573)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2010: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2008: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 薬物動態 / 遺伝子 / コピー数多型 / CNV / 薬剤反応性 / PK / PD遺伝子 / 肺癌

Research Abstract

We developed a new method for the analysis of CNV, and analyzed of CNV in PK/PD-related genes in healthy volunteers and NSCLC patients. The new method, using real-time PCR and calibrator vector, was high-throughput to determine the absolute copy number, and it was expected to suit for the clinical diagnosis. But, it is necessary to take account of the localization of target sequence of primer and probes. We detected some new CNV in PK/PD related genes. As the result of the analysis in detail, some may change the function of the gene. The clinical impacts of CNV should be cleared by further investigations.

Research Products

• [Journal Article] Systematic screening of human ABCC3 polymorphisms and their effects on MRP3 expression and function. (2011)
  • Author(s): Sasaki T, Hirota T, Ryokai Y, Kobayashi D, Kimura M, Irie S, Higuchi S, Ieiri I.
  • Journal Title: Drug Metab Pharmacokinet. Apr22
  • NAID: 130004463197
  • Peer Reviewed
• [Journal Article] Novel large-scale deletion (whole exon 7) in the ABCC2 gene in a patient with the Dubin-Johnson syndrome. (2009)
  • Author(s): Kanda D, Takagi H, Kawahara Y, Yata Y, Takakusagi T, Hatanaka T, Yoshinaga T, Iesaki K, Kashiwabara K, Higuchi T, Mori M, Hirota T, Higuchi S, Ieiri I.
  • Journal Title: Drug Metab Pharmacokinet. 24(5) Pages: 464-468
  • NAID: 130004463097
  • Peer Reviewed
• [Presentation] Pharmacogenomics of Drug Transporters in Humans. (2010)
  • Author(s): Ieiri Ichiro
  • Organizer: 18^<th> International Symposium on Microsomes and Drug Oxidations
  • Place of Presentation: Beijing (China)
  • Year and Date: 2010-05-19
• [Presentation] 非小細胞肺癌における抗がん剤の代謝・輸送関連遺伝子の遺伝子発現とCopy Number Variation解析 (2009)
  • Author(s): 近森綾子
  • Organizer: 第26回日本薬学会九州支部大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-12-13
• [Presentation] 薬物動態関連遺伝子のCopy Number Variation解析とその活用における留意点日本薬学会 (2009)
  • Author(s): 家入一郎、木下智広、廣田豪、安東幸恵、樋口駿
  • Organizer: 第129回年会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2009-03-28
• [Presentation] Real Time PCR法を用いた薬物動態関連遺伝子のCopy Number Variation (CNV)解析 (2008)
  • Author(s): 木下智広、廣田豪、安東幸恵、家入一郎、樋口駿
  • Organizer: 第25回日本薬学会九州支部大会
  • Place of Presentation: 九州保健福祉大学薬学部
  • Year and Date: 2008-12-07
• [Presentation] Determination of CYP2D6 copy number variation by real-time quantitative PCR in Japanese. (2008)
  • Author(s): 安東幸恵, 木下智広, 廣田豪, 樋口駿, 家入一郎
  • Organizer: 2^<nd> Asian Pacific ISSX Regional Meeting
  • Place of Presentation: School of pharmacy, Fudan University
  • Year and Date: 2008-05-13
• [Book] 抗癌剤のPK/PD関連遺伝子におけるコピー数多型と遺伝子発現の臨床的意義の評価 修士論文 (2010)
  • Author(s): 近森綾子
• [Book] Real-time PCR法を用いたpharmacokinetics/pharmacodynamics関連遺伝子のCopy Number Variation (CNV)解析修士論文 (2009)
  • Author(s): 木下智広