Interindividual variations of flavin-containing monooxygenase 3 (FMO3) related to menstruation

• Project/Area Number: 19790134
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: SHIMIZU Makiko Showa Pharmaceutical University, 薬学部, 助教 (90307075)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,570,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: FMO3 / trimethylaminuria / genetic polymorphism / Japanese / menstruation / 個人差 / 5'-上流領域 / 転写因子 / 遺伝子多型 / ハプロタイプ / FM03 / 転写調節

Research Abstract

化学物質の生体内運命を理解する上で重要な薬物代謝酵素としてFMO3 を、化学物質としてトリメチルアミンを取り上げ、その個人差に影響を及ぼす要因についてまとめた。トリメチルアミンの酸化的代謝に関わるFMO3の個人間変動は量的には核内調節因子などの制御を受け、質的にはFMO3遺伝子変異の影響を受けていることが明らかとなった。FMO3の個人内変動の要因としては女性ホルモンなどによる量的変化の可能性が推察された。すなわち、FMO3の個人間および個人内変動が化学物質トリメチルアミンの生体内運命を規定していた。

Research Products

• [Journal Article] Drug interactions of thalidomide with midazolam and cyclosporine A: heterotropic cooperativity of human cytochrome P450 3A5 (2009)
  • Author(s): Okada, Y., Murayama, N., Yanagida, C., Shimizu, M., Guengerich, F.P., and Yamazaki, H
  • Journal Title: Drug Metab.Dispos 37 Pages: 18-23
  • Peer Reviewed
• [Journal Article] トリメチルアミン尿症(魚臭症候群)に関わる薬物酸化酵素フラビン含有モノオキシゲナーゼ3のゲノム薬理学 (2009)
  • Author(s): 山崎浩史,清水万紀子
  • Journal Title: 臨床薬理 40
  • NAID: 10026442304
• [Journal Article] Inter-individual variations of flavin-containing monooxygenase 3 in livers from Japanese : correlation with hepatic transcription factors (2009)
  • Author(s): Nagashima, S., Shimizu, M., Yano, H., Murayama, N., Kumai, T., Kobayashi, S., Guengerich, F.P., and Yamazaki, H.
  • Journal Title: Drug Metab. Pharmacokinet (In press)
  • NAID: 10025723470
  • Peer Reviewed
• [Journal Article] Increased distribution of carboplatin, an anti-cancer agent, to rat brains with aid of hyperbaric oxygenation (2008)
  • Author(s): Suzuki, Y., Tanaka, K., Negishi, D., Shimizu, M., Murayama, N., Hashimoto, T. and Yamazaki, H
  • Journal Title: Xenobiotica 38 Pages: 1471-1475
  • Peer Reviewed
• [Journal Article] Increased transendothelial permeability of anti-cancer agent carboplatin with aid of hyperbaric oxygenation (2008)
  • Author(s): Yamazaki, H., Shimizu, M., Murayama, N., Tanaka, K., Nion, S., a nd Cecchelli, R.
  • Journal Title: Xenobiotica 38 Pages: 1298-1304
  • Peer Reviewed
• [Journal Article] Complex mechanism underlying transcriptional control of the haplotyped flavin-containing monooxygenase 3 (FMO3) gene in Japanese : Different regulation between mutations in 5'-upstream d istal region and common element in proximal region (2008)
  • Author(s): Shimizu, M., Murayama, N., Nagashima, S., Fujieda, M. and Yamazaki, H
  • Journal Title: Drug Metab. Pharmacokinet 23 Pages: 54-58
  • NAID: 10024187751
  • Peer Reviewed
• [Journal Article] Complex mechanism underlying transcriptional control of the haplotyped flavin-containing monooxygenase 3 (FMO3) gene in Japanese : Different regulation between mutations in 5'-upstream distal region and common element in proximal region (2008)
  • Author(s): Shimizu, M., Murayama, N., Nagashima, S., Fujieda, M. and Yamazaki, H.
  • Journal Title: Drug Metab.Pharmacokinet 23 Pages: 54-58
  • NAID: 10024187751
  • Peer Reviewed
• [Journal Article] Increased transendothelial permeability of anti-cancer agent carboplatin with the aid of hyperbaric oxygenation (2008)
  • Author(s): Yamazaki, H., Shimizu, M., Murayama, N., Tanaka, K., Nion, S., and Cecchelli, R.
  • Journal Title: Xenobiotica 38 Pages: 1298-1304
  • Peer Reviewed
• [Journal Article] Involvement of human cytochrome P450 2B6 in the ω- and 4-hydroxylation of the anesthetic agent propofol (2007)
  • Author(s): Murayama, N., Minoshima, M., Shimizu, M., Guengerich, F.P., and Yamazaki, H
  • Journal Title: Xenobiotica 37 Pages: 717-724
  • Peer Reviewed
• [Journal Article] Molecular evolution and balancing selection in the flavin-containing monooxygenase 3 gene (FMO3) (2007)
  • Author(s): Allerston, C.K., Shimizu, M., Fujieda, M. Shephard, E.A. Yamazaki, H. and Phillips, I.R.
  • Journal Title: Pharmacogenet.Genomics 17 Pages: 827-839
  • Peer Reviewed
• [Journal Article] Roles of CYP3A4 and CYP2C19 in methylhydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes (2007)
  • Author(s): Murayama, N., Imai, N., Nakane, T., Shimizu, M., and Yamazaki, H
  • Journal Title: Biochem.Pharmacol 73 Pages: 2020-2026
  • Peer Reviewed
• [Journal Article] Transient trimethylaminuria related to menstruation (2007)
  • Author(s): Shimizu, M., Cashman, J.R. and Yamazaki, H
  • Journal Title: BMC. Med. Genet 8 Pages: 2-2
  • Peer Reviewed
• [Journal Article] Effects of propofol analogs on glucuronidation of propofol, an anesthetic drug, by human liver microsomes (2007)
  • Author(s): Shimizu, M., Matsumoto, Y., and Yamazaki, H
  • Journal Title: Drug Metab.Lett 1 Pages: 77-79
  • Peer Reviewed
• [Journal Article] Missense and Nonsense Mutations of the Flavin-containing Monooxygenase 3 Gene in a Japanese Cohort, Drug Metab (2007)
  • Author(s): Shimizu, M., Tomioka, S., Murayama, N., and Yamazaki, H
  • Journal Title: Pharmacokinet 22 Pages: 61-64
  • Peer Reviewed
• [Journal Article] Stop codon mutations in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population (2007)
  • Author(s): Yamazaki, H., Fujita, H., Gunji, T., Zhang, Z., Kamataki, T., Cashman, J.R., Shimizu, M
  • Journal Title: Mol. Genet. Metab 90 Pages: 58-63
  • NAID: 120000971644
  • Peer Reviewed
• [Journal Article] Genetic polymorphism of the flavin-containing monooxygenase 3 (FMO3) associated with trimethylaminuria (fish odor syndrome): Observations from Japanese patients (2007)
  • Author(s): Yamazaki H., and Shimizu, M
  • Journal Title: Current Drug Metabolism 8 Pages: 487-491
  • Peer Reviewed
• [Journal Article] Stop codon mutations in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population. (2007)
  • Author(s): Yamazaki, H・Fujita, H・Gunji, T・Zhang, Z・Kamataki, T・Cashman, JR・Shimizu, M.
  • Journal Title: Mol. Genet. Metab. 90 Pages: 58-63
  • NAID: 120000971644
  • Peer Reviewed
• [Journal Article] Effect of genetic variants of the human falvin-containing monooxygenase 3 (FMO3) on N-and S-oxygenation activities. (2007)
  • Author(s): Shimizu, M.・Yano, H.・Nagashima, S.・Murayama, N.・Zhang, J.・Cashman, J.R.・Yamazaki, H.
  • Journal Title: Drug Metab. Dispos. 35 Pages: 328-330
  • Peer Reviewed
• [Journal Article] Molecular evolution and balancing selection in the flavin-contatining monooxygenase 3 gene (FMO3). (2007)
  • Author(s): Allerston, C.K.・Shimizu, M.・Fujieda, M.・Shephard, E.A.・Yamazaki, H.・Phillips, I.R.
  • Journal Title: Pharmacogenet.Genomics 17 Pages: 827-839
  • Peer Reviewed
• [Journal Article] Inter-individual variations of flavin-containing monooxygenase 3 in livers from Japanese: correlation with hepatic transcription factors
  • Author(s): Nagashima, S., Shimizu, M., Yano, H., Murayama, N., Kumai, T., Kobayashi, S., Guengerich, F.P., and Yamazaki, H.
  • Journal Title: Drug Metab.Pharmacokin (in press)
  • NAID: 10025723470
  • Peer Reviewed
• [Journal Article] Effect of genetic variants of the human flavin-containing monooxygenase 3 (FMO3) on N- and S-oxygenation activities
  • Author(s): Shimizu, M., Yano, H., Nagashima, S., Murayama, N., Zhang, J., Cashman, J.R. and Yamazaki, H
  • Journal Title: Drug Metab. Dispos 35 Pages: 328-330
  • Peer Reviewed
• [Presentation] 日本人のフラビン含有モノオキシゲナーゼ3(FMO3)ハプロタイプの解析 (2009)
  • Author(s): 清水万紀子、永島里美、村山典恵、山崎浩史
  • Organizer: 日本薬学会第129回年会
  • Place of Presentation: 京都
• [Presentation] フラビン含有モノオキシゲナーゼ3変異酵素の医薬品参加酵素活性 (2009)
  • Author(s): 永島里美、清水万紀子、村山典恵、山崎浩史
  • Organizer: 日本薬学会第129回年会
  • Place of Presentation: 京都
• [Presentation] Expression levels and catalytic activities of flavin-containing monooxygenase 3 in Japanese and Caucasian livers (2008)
  • Author(s): Makiko Shimizu, Satomi Nagashima, Norie Murayama, Hiroshi Yamazaki
  • Organizer: International Society for the Study of Xenobiotics 15th North American Regional Meeting
  • Place of Presentation: San Diego
• [Presentation] Makiko Shimizu, Satomi Nagashima, Norie Murayama, Hiroshi Yamazaki (2008)
  • Author(s): Makiko Shimizu, Satomi Nagashima, Norie Murayama, Hiroshi Yamazaki
  • Organizer: 23rd JSSX Annual Meeting
  • Place of Presentation: kumamoto
• [Presentation] ヒト肝フラビン含有モノオキシゲナーゼ3発現に影響する因子の解析 (2008)
  • Author(s): 永島里美、清水万紀子、矢野裕士、村山典恵、山崎浩史
  • Organizer: 医療薬学フォーラム2008,第16回クリニカルファーマシーシンポジウム
• [Presentation] トリメチルアミン尿症が疑われる日本人の対症療法の検討、医療薬学フォーラム2008 (2008)
  • Author(s): 清水万紀子、野村里香、小園真里恵、永島里美、村山典恵、山崎浩史
  • Organizer: 第16回クリニカルファーマシーシンポジウム
• [Presentation] Analysis of Suppression and activation of the haplotyped flavin-containing monooxygenase 3 (FMO3) Gene Transcriptions in Japanese (2008)
  • Author(s): Makiko Shimizu, Norie Murayama, Satomi Nagashima, Masaki Fujieda, and Hiroshi Yamazaki
  • Organizer: 2nd Asia Pacific ISSX Meeting 2008
  • Place of Presentation: Shanghai, China
• [Presentation] レポーターアッセイを用いたヒトFMO3遺伝子の転写調節機構の解析 (2008)
  • Author(s): 清水万紀子,永島里美,村山典惠,山崎浩史
  • Organizer: 日本薬学会第127回年会
  • Place of Presentation: 横浜
• [Presentation] ヒト肝におけるフラビン含有モノオキシゲナーゼ3発現量の個人差の解析 (2008)
  • Author(s): 永島里美,清水万紀子,矢野裕士,村山典惠,山崎浩史
  • Organizer: 日本薬学会第127回年会
  • Place of Presentation: 横浜
• [Presentation] Catalitic activities of the flavin-containing monooxygenase 3 (FMO3) variants found in Japanese (2008)
  • Author(s): Satomi Nagashima, Makiko Shimizu, Hiroshi Yano, Norie Murayama, and Hiroshi Yamazaki
  • Organizer: Pan-Pacific International Partnership Conference on Pharmaceutical and Life Sciences
  • Place of Presentation: Nagoya
• [Presentation] Individual Difference of Flavin-Containing Monooxygenase3 in Human Livers (2008)
  • Author(s): Shimizu, M., Nagashima, S., Murayama, N., and Yamazaki, H
  • Organizer: 23rd JSSX Annual Meeting
  • Place of Presentation: 熊本
• [Presentation] 薬物代謝酵素フラビン含有モノオキシゲナーゼがもたらすアミン化合物酸化的代謝の個人差に関する臨床薬理学研 (2007)
  • Author(s): 山崎浩史、清水万紀子、永島里美、村山典惠
  • Organizer: 28回日本臨床薬理学会年会
  • Place of Presentation: 栃木
• [Presentation] Genetic Polymorphism of the Flavin-Containing Monooxygenase 3 (FMO3) Associated with Trimethylaminuria in a Japanese Cohort (2007)
  • Author(s): Makiko Shimizu, Satomi Nagashima, Norie Murayama and Hiroshi Yamazaki
  • Organizer: 22nd JSSX/ 8th ISSX meeting
  • Place of Presentation: Sendai
• [Presentation] Oxygenation Activities of the Flavin-Containing Monooxygenase 3 (FMO3) Variants Found in Japanese (2007)
  • Author(s): Satomi Nagashima, Makiko Shimizu, Hiroshi Yano, Norie Murayama, and Hiroshi Yamazaki
  • Organizer: 22nd JSSX/ 8th ISSX meeting
  • Place of Presentation: Sendai
• [Presentation] Genetic Polymorphism of the Flavin-Containing Moonooxygenase 3(FMO3) Associated with Trimethylaminuria in a Japanese Cohort (2007)
  • Author(s): Shimizu, M.・Nagashima, S.・Murayama, N.・Yamazaki, H.
  • Organizer: 22nd JSSX/8th ISSX meeting
  • Place of Presentation: Sendai
• [Book] 臨床薬理の進歩No.29 (2008)
  • Author(s): 山崎浩史、清水万紀子、永島里美、村山典恵
  • Publisher: 臨床薬理研究振興財団
• [Book] 臨床薬理の進歩 (2008)
  • Author(s): 山崎浩史、清水万紀子、永島里美、村山典恵
  • Total Pages: 6
  • Publisher: 薬物代謝酵素フラビン含有モノオキシゲナーゼがもたらすアミン化合物酸化的代謝の個人差に関する研究