The role of GIRK channel gene polymorphisms in the individual differences in sensitivity to analgesics

• Project/Area Number: 20602020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 疼痛学
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: NISHIZAWA DAISUKE Tokyo Metropolitan Organization for Medical Research, 東京都精神医学総合研究所, 流動研究員 (80450584)
• Co-Investigator(Kenkyū-buntansha): IKEDA Kazutaka 財団法人東京都医学研究機構, 東京都精神医学総合研究所, 副参事研究員 (60281656)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 鎮痛薬感受性個人差 / GIRKチャネル / 遺伝子多型 / 薬理遺伝学 / 個別化医療 / 関連研究

Research Abstract

In association studies targeting genetic polymorphisms identified in brain-type GIRK1-GIRK3 genes, significant associations were found between the GIRK3 C1339T, C1781T and C1817T polymorphisms and requirements of postoperative 24-h opioid analgesics after major open abdominal surgery or painful orofacial cosmetic surgery. In particular, there were significant associations in the C1781T and C1817T between analgesic requirements and mRNA expressions, suggesting that the GIRK3 mRNA expression could affect the analgesic effects of opioids.

Research Products

• [Journal Article] Identification of Selective Agonists and Antagonists to Gn Protein-Activated Inwardly Rectifying Potassium Channels: Potassium Channels : Candidate Medicines for Drug Dependence and Pain (2011)
  • Author(s): Nishizawa D, Gajya N, Ikeda K
  • Journal Title: Current Neuropharmacology Vol.9 Pages: 113-117
• [Journal Article] Identification of Selective Agonists and Antagonists to G Protein-Activated Inwardly Rectifying Potassium Channels : Candidate Medicines for Drug Dependence and Pain (2011)
  • Author(s): Nishizawa D, Gajya N, Ikeda K
  • Journal Title: Current Neuropharmacology Volume: 9 Pages: 113-117
• [Journal Article] Inhibition of G protein-activatedinwardly rectifying K+ channels by phencyclidine (2011)
  • Author(s): Kobayashi T, Nishizawa D, Ikeda K
  • Journal Title: Current Neuropharmacology Volume: 9 Pages: 244-246
• [Journal Article] Association between KCNJ6 ( GIRK2) Gene polymorphisms and postoperative analgesic requirements after major abdominal surgery (2009)
  • Author(s): Nishizawa D, Nagashima M, Katoh R, Satoh Y, Tagami M, Kasai S, Ogai Y, Han W, Hasegawa J, Shimoyama N, Sora I, Hayashida M, Ikeda K
  • Journal Title: PLoS ONE 4巻
  • Peer Reviewed
• [Journal Article] 遺伝子多型と疼痛感受性,オピオイド感受性-基礎および臨床のデータから- (2009)
  • Author(s): 西澤大輔,長島誠,佐藤泰雄,田上惠,池田和隆
  • Journal Title: 麻酔 58巻 Pages: 1093-1101
  • Peer Reviewed
• [Journal Article] Association between KCNJ6(GIRK2)Gene polymorphisms and postoper ative analgesic requirements after major abdominal surgery (2009)
  • Author(s): Nishizawa D, Nagashima M, Katoh R, Satoh Y, Tagami M, Kasai S, Ogai Y, Han W, Hasegawa J, Shimoyama N, Sora I, Hayashida M, Ikeda K
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] Genetic polymorphisms and human sensitivity to opioid analgesics (2009)
  • Author(s): Nishizawa D, Hayashida M, Nagashima M, Koga H, Ikeda K
  • Journal Title: In : Methods in Molecular Biology Pages: 395-420
• [Journal Article] Potassium channels (2009)
  • Author(s): Nishizawa D, Kobayashi T, Ikeda K
  • Journal Title: In : Peripheral receptor targets for analgesia : Novel approaches to pain treatment Pages: 93-110
• [Journal Article] 遺伝子多型と疼痛感受性, オピオイド感受性-基礎および臨床のデータから- (2009)
  • Author(s): 西澤大輔, 長島誠, 佐藤泰雄, 田上惠, 池田和隆
  • Journal Title: 麻酔 58 Pages: 1093-1101
  • Peer Reviewed
• [Presentation] Association between GIRK3 gene polymorphisms and postoperative analgesic requirements after major abdominal surgery (2010)
  • Author(s): Nishizawa D, Nagashima M, Kato R, Sato Y, Tagami M, Kasai S, Ogai Y, Hasegawa J, Hayashida M, Ikeda K
  • Organizer: The American Society of Human Genetics 60th Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-11-03
• [Presentation] 遺伝子解析による術後疼痛、がん性疼痛マネジメントへの貢献 (2010)
  • Author(s): 西澤大輔,池田和隆
  • Organizer: 第4回日本緩和医療薬学会年会
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-09-25
• [Presentation] 痛覚感受性個人差の遺伝要因 (2010)
  • Author(s): 池田和隆, 西澤大輔, 笠井慎也
  • Organizer: 第4回日本緩和医療薬学会年会
  • Place of Presentation: 鹿児島(招待講演)
  • Year and Date: 2010-09-25
• [Presentation] 遺伝子解析による術後疼痛、がん性疼痛マネジメントへの貢献 (2010)
  • Author(s): 西澤大輔, 池田和隆
  • Organizer: 第4回日本緩和医療薬学会年会
  • Place of Presentation: 鹿児島(招待講演)
  • Year and Date: 2010-09-25
• [Presentation] GIRKチャネルサブユニットGIRK3の遺伝子多型と開腹術後鎮痛との関連 (2010)
  • Author(s): 西澤大輔,長島誠,加藤良二,佐藤泰雄,田上惠,笠井慎也,大谷保和,長谷川準子,林田眞和,池田和隆
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台
  • Year and Date: 2010-09-17
• [Presentation] GIRKチャネルサブユニットGIRK3の遺伝子多型と開腹術後鎮痛との関連 (2010)
  • Author(s): 西澤大輔, 長島誠, 加藤良二, 佐藤泰雄, 田上惠, 笠井慎也, 大谷保和, 長谷川準子, 林田眞和, 池田和隆
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台(宮城)
  • Year and Date: 2010-09-17
• [Presentation] オピオイド感受性個人差と遺伝子多型 (2010)
  • Author(s): 池田和隆, 西澤大輔, 福田謙一, 林田眞和
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台(宮城)
  • Year and Date: 2010-09-15
• [Presentation] Polymorphisms of the genes encoding the mu-opioid receptor and GIRK2 ( KCNJ6) are associated with postoperative opioid requirements (2010)
  • Author(s): Ikeda K, Nishizawa D, Kasai S, Fukuda K, Hayashida M
  • Organizer: CINP 2010
  • Place of Presentation: Hong kong
  • Year and Date: 2010-06-08
• [Presentation] Polymorphisms of the genes encoding the mu-opioid receptor and GIRK2 (KCNJ6) are associated with postoperative opioid requirements (2010)
  • Author(s): Ikeda K, Nishizawa D, Kasai S, Fukuda K, Hayashida M
  • Organizer: CINP 2010
  • Place of Presentation: Hong kong
  • Year and Date: 2010-06-08
• [Presentation] GIRKチャネル遺伝子GIRK2の遺伝子多型と開腹術後鎮痛との関連 (2009)
  • Author(s): Nishizawa D, Nagashima M, Katoh R, Satoh Y, Tagami M, Kasai S, Ogai Y, Han W, Hasegawa J, Shimoyama N, Sora I, Hayashida M, Ikeda K
  • Organizer: 第39回日本神経精神薬理学会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-14
• [Presentation] GIRKチャネル遺伝子GIRK2の遺伝子多型と開腹術後鎮痛との関連 (2009)
  • Author(s): Daisuke Nishizawa, Makoto Nagashima, Ryoji Katoh, Yasuo Satoh, Megumi Tagami, Shinya Kasai, Yasukazu Ogai, Wenhua Han, Junko Hasegawa, Naohito Shimoyama, Ichiro Sora, Masakazu Hayashida, Kazutaka Ikeda
  • Organizer: 第19回日本臨床精神神経薬理学会・第39回日本神経精神薬理学会合同年会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-14
• [Presentation] A genome-wide association study on opioid analgesic sensitivity in patients undergoing painful cosmetic surgery (2009)
  • Author(s): Daisuke Nishizawa, Kenichi Fukuda, Shinya Kasai, Wenhua Han, Junko Hasegawa, Akinori Nishi, Minori Koga, Tadao Arinami, Masakazu Hayashida, Kazutaka Ikeda
  • Organizer: The American Society of Human Genetics 59th Annual Meeting
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2009-10-22
• [Presentation] ゲノムワイド関連解析によるオピオイド鎮痛薬感受性関連遺伝子多型の網羅的探索 (2009)
  • Author(s): 西澤大輔, 福田謙一, 笠井慎也, 韓文華, 長谷川準子, 西明紀, 古賀農人, 有波忠雄, 林田眞和, 池田和隆
  • Organizer: 日本人類遺伝学会第54回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-24
• [Presentation] Association of GIRK3 gene polymorphisms with methamphetamine and alcohol dependence (2008)
  • Author(s): Nishizawa D
  • Organizer: The American Society of Human Genetics 58th Annual Meeting
  • Place of Presentation: Philadelphia
  • Year and Date: 2008-11-12
• [Presentation] GIRKチャネル遺伝子GIRK3の遺伝子多型とメタンフェタミン依存症及びアルコール依存症との関連 (2008)
  • Author(s): Nishizawa D
  • Organizer: 第18回日本臨床精神神経薬理学会・第38回日本神経精神薬理学会 合同年会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-02
• [Book] Methods in Molecular Biology(Genetic polymorphisms and human sensitivity to opioid analgesics) (2010)
  • Author(s): Nishizawa D, Hayashida M, Nagashima M, Koga H, Ikeda K
  • Publisher: Totowa : The humana press Inc.
• [Book] Genetic polymorphisms and human sensitivity to opioid analgesics.In : Methods in Molecular Biology (Arpad Szallasi, ed) (2010)
  • Author(s): Nishizawa D, Hayashida M, Nagashima M, Koga H, Ikeda K
  • Publisher: Totowa : The humana press Inc.
• [Patent(Industrial Property Rights)] Method of evaluating drug-sensitivity by analyzing the GIRK channel genes (2010)
  • Inventor(s): Ikeda K, Hayashida M, 西澤大輔,Sora I
  • Industrial Property Rights Holder: 財団法人東京都医学研究機構
  • Filing Date: 2010-09-06
  • Overseas
• [Patent(Industrial Property Rights)] Method of evaluating drug-sensitivity by analyzing the GIRK channel genes (2010)
  • Inventor(s): Ikeda K, Hayashida M, 西澤大輔,Sora I
  • Industrial Property Rights Holder: 財団法人東京都医学研究機構
  • Filing Date: 2010-07-28
  • Overseas
• [Patent(Industrial Property Rights)] Method of evaluating drug-sensitivity by analyzing the GIRK channel genes (2010)
  • Inventor(s): Ikeda K, Hayashida M, 西澤大輔,Sora I
  • Industrial Property Rights Holder: 財団法人東京都医学研究機構
  • Filing Date: 2010-07-17
  • Overseas
• [Patent(Industrial Property Rights)] Method of evaluating drug-sensitivity by analyzing the GIRK channel genes (2010)
  • Inventor(s): Ikeda K, Hayashida M, 西澤大輔,Sora I
  • Industrial Property Rights Holder: 財団法人東京都医学研究機構
  • Filing Date: 2010-07-14
  • Overseas