Are protein expression levels changed by intron SNPs on CYP2D6?

• Project/Area Number: 23659070
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: HIRATSUKA Masahiro 東北大学, 大学院・薬学研究科, 准教授 (50282140)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Aki 東北大学, 大学院・薬学研究科, 助手 (30545695)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 薬物動態 / 代謝学 / CYP2D6 / ファーマコゲノミクス

Research Abstract

We examined changes in the protein expression of the drug-metabolizing enzyme CYP2D6 by using an assay capable of analyzing the influence of intron SNPs, to determine the individual differences in protein activity that cannot be explained by exon SNPs alone. As a result, we found that while the positive control CYP2D6*41 showed a 35% decrease in protein expression compared to the wild-type CYP2D6*1, none of the other 4 variants differed greatly from the wild-type.

Research Products

• [Journal Article] In vitro assessment of the allelic variants of cytochrome P450 (2012)
  • Author(s): Masahiro Hiratsuka
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 27 Pages: 68-84
  • NAID: 130004463230
  • Peer Reviewed
• [Journal Article] Ilse van der Heiden, Ron HN van Schaik, Jan Jakobsson, Magnus Ingelman-Sundberg. Influence of sex on propofol metabolism, a pilot study: implications for propofol anesthesia (2012)
  • Author(s): Irena Loryan, Marja Lindqvist, Inger Johansson, Masahiro Hiratsuka
  • Journal Title: Eur. J. Clin. Pharmacol Volume: 68 Issue: 4 Pages: 397-406
  • DOI: 10.1007/s00228-011-1132-2
  • Peer Reviewed
• [Journal Article] In Vitro Assessment of the Allelic Variants of Cytochrome P450 (2012)
  • Author(s): Masahiro Hiratsuka
  • Journal Title: Drug Metabolism and Pharmacokinetics Volume: 27 Issue: 1 Pages: 68-84
  • DOI: 10.2133/dmpk.DMPK-11-RV-090
  • NAID: 130004463230
  • ISSN: 1347-4367, 1880-0920
  • Peer Reviewed
• [Journal Article] Influence of sex on propofol metabolism (2012)
  • Author(s): Masahiro Hiratsuka et al
  • Journal Title: Eur. J. Clin. Pharmacol. Volume: 68 Pages: 397-406
  • Peer Reviewed
• [Journal Article] In vitro assessment of the allelic variants (2012)
  • Author(s): Masahiro Hiratsuka
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 27 Pages: 68-84
  • Peer Reviewed
• [Journal Article] Functional characterization of CYP2B6 allelic variants in demethylation of anti-malarial artemethe (2011)
  • Author(s): Honda, M., Muroi, Y., Tamaki, Y., Saigusa, D., Suzuki, N., Tomioka, Y., Matsubara Y., Oda, A., Hirasawa, N., Hiratsuka, M.
  • Journal Title: Drug Metab. Dispos Volume: 39 Issue: 10 Pages: 1860-1865
  • DOI: 10.1124/dmd.111.040352
  • Peer Reviewed
• [Journal Article] Association between cancer risk and drug metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in Japanese cases of lung cancer (2011)
  • Author(s): Yuichiro Tamaki, Tomio Arai, Haruhiko Sugimura, Takamitsu Sasaki, Masashi Honda, Yuka Muroi, Yoichi Matsubara, Shuichi Kanno, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka
  • Journal Title: Drug Metab. Pharmacokinet Volume: 26 Pages: 516-522
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21791872
  • Peer Reviewed
• [Journal Article] Novel single nucleotide polymorphism of CYP2A13 gene in a Japanese population (2011)
  • Author(s): Yuichiro Tamaki, Masashi Honda, Yuka Muroi, Tomio Arai, Haruhiko Sugimura, Yoichi Matsubara, Shuichi Kanno, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 26 Pages: 544-547
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21606606
  • Peer Reviewed
• [Journal Article] Novel single nucleotide polymorphism of CYP2A13 (2011)
  • Author(s): Masahiro Hiratsuka et al
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 26 Pages: 544-547
  • Peer Reviewed
• [Journal Article] Association between cancer risk (2011)
  • Author(s): Masahiro Hiratsuka et al
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 26 Pages: 516-522
  • Peer Reviewed
• [Journal Article] Functional characterization of CYP2B6 (2011)
  • Author(s): Masahiro Hiratsuka et al
  • Journal Title: Drug Metab. Dispos. Volume: 39 Pages: 1860-1865
  • Peer Reviewed
• [Presentation] ファーマコゲノミクス解析による個別化薬物療法の推進 (2012)
  • Author(s): 平塚真弘
  • Organizer: 第22回日本医療薬学会年会
  • Place of Presentation: 新潟
  • Year and Date: 2012-10-28
• [Presentation] 遺伝子多型情報に基づく薬物代謝酵素バリアントの酵素反応速度論的機能解析 (2011)
  • Author(s): 平塚真弘
  • Organizer: 日本薬学会東北支部第10回医療系薬学若手研究者セミナー
  • Place of Presentation: 東北大学
  • Year and Date: 2011-09-17
• [Presentation] 遺伝子多型情報に基づく薬物代謝酵素バリアントの酵素反応速度論的機能解析
  • Author(s): 平塚真弘
  • Organizer: 日本薬学会東北支部 第10回医療系薬学若手研究者セミナー(招待講演)
  • Place of Presentation: 仙台