The influence based on CYP3A5 gene polymorphism for calcineurin inhibitors for tailor-made treatment after living-donor liver transplantation.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591521
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Mie University
• Principal Investigator: USUI Masanobu Mie University, 大学院・医学系研究科, 講師 (10378341)
• Co-Investigator(Kenkyū-buntansha): SUGIMOTO Kazushi 三重大学, 医学部附属病院, 助教 (60378370)
• Project Period (FY): 2008 – 2010
• Keywords: 生体肝移植 / CYP3A5 / 遺伝子多型 / テーラーメード治療

Research Abstract

Pharmacokinetics of tacrolims in transplantation, especially a body-weight-based dose, often result in marked individual diversity of blood drug concentration. Tacrolimus is a substrate for cytochrome P450(CYP)3A5 having polymorphism. In this study, we genotyped CYP3A5 polymorphism and investigated the association between donor/recipient polymorphisms and pharmacokinetics of tacrolimus in living-donor liver transplantation (LDLT). Furthermore we are trying to introduce a tailor-made therapy based on the donor/recipient CYP3A5 polymorphisms. CYP3A5 polymorphism in the recipient as well as the donor highly influences pharmacokinetics of tacrolimus in the LDLT for the long term. Tailor-made treatment based on CYP3A5 genotype is effective to the reduction of the tacrolimus administration, which may reduce the incidence of drug side effect and ACR.

Research Products

• [Journal Article] J Hepatobiliary Pancreat Sci. (2011)
  • Author(s): Mizuno S, Hamada T, Nakatani K, Kishiwada M, Usui M, Sakurai H, Tabata M, Sakamoto Y, Nishioka J, Muraki Y, Okuda M, Nobori T, Isaji S.
  • Journal Title: 18(2) Pages: 226-232,232-234
  • Peer Reviewed
• [Journal Article] 肝移植後のB型肝炎再発予防の現状-特にワクチン継続接種の効果- (2011)
  • Author(s): 臼井正信、水野修吾、伊佐地秀司
  • Journal Title: 今日の移植 vol24 Pages: 78-83
• [Journal Article] Effect of a prostaglandin I(2) analog on the expression of thrombomodulin in liver and spleen endothelial cells after an extensive hepatectomy. (2010)
  • Author(s): Usui M, Kuriyama N, Kisawada M, Hamada T, Mizuno S, Sakurai H, Tabata M, Isaji S.
  • Journal Title: Surg.Today 41 Pages: 230-236
  • Peer Reviewed
• [Journal Article] Tissue factor expression demonstrates severe sinusoidal endothelial cell damage during rejection after living-donorliver transplantation. (2009)
  • Author(s): Usui M, Kuriyama N, Kisawada M, Hamada T, Mizuno S, Sakurai H, Tabata M, Okamoto K, Uemoto S, Isaji S.
  • Journal Title: JHepatobiliary Pancreat Surg 16 Pages: 513-520
  • Peer Reviewed
• [Presentation] タクロリムス持続静注による肝移植周術期管理-遺伝子多型の影響- (2011)
  • Author(s): 臼井正信、村木優一、大倉康生、熊本幸司、岸和田昌之、大澤一郎、濱田賢司、水野修吾、櫻井洋至、田端正己、伊佐地秀司、奥田真弘
  • Organizer: 肝移植術後管理検討会
  • Place of Presentation: 京都
  • Year and Date: 2011-01-29
• [Presentation] Thrombomodulin and Tenascin C levels in the blood are good predictive markers for the outcome after living donor liver transplantation. (2010)
  • Author(s): Usui M, Kuriyama N, Kisawada M, Hamada T, Mizuno S, Sakurai H, Tabata M, Isaji S
  • Organizer: American Transplant Congress
  • Place of Presentation: San Diego, USA
  • Year and Date: 20100501-20100504
• [Presentation] 大建中湯は生体肝移植術後の門脈血流改善効果に加えbacterial translocation制御に有効か (2010)
  • Author(s): 臼井正信、大倉康生、熊本幸司、岸和田昌之、大澤一郎、濱田賢司、水野修吾、櫻井洋至、田端正己、伊佐地秀司
  • Organizer: 日本消化器外科学会
  • Place of Presentation: 下関
  • Year and Date: 2010-07-16
• [Presentation] パネルディスカッション9肝移植後の長期成績と問題点.生体肝移植後の長期成績-C型肝炎再発に対するIFN治療の長期成績について- (2009)
  • Author(s): 臼井正信、大倉康生、熊本幸司、岸和田昌之、大澤一郎、濱田賢司、水野修吾、櫻井洋至、田端正己、伊佐地秀司
  • Organizer: 日本消化器外科学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-07-18
• [Presentation] Long-term influence of CYP3A5 donor/recipient polymorphism on the pharmacokinetics of calcineurin inhibitors in the recipients of living-donor liver transplantation (2009)
  • Author(s): Usui M, Muraki Y, Kato H, Kuriyama N, Kishiwada M, Mizuno S, Sakurai H, Tabata M, Okuda M, Nishioka J, Nakatani A, Nobori T, Isaji S
  • Organizer: Transplant Congress
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-05-30
• [Presentation] 遺伝子情報に基づいた生体肝移植における免疫抑制剤の最適化への取り組み (2009)
  • Author(s): 臼井正信、村木優一、大倉康生、熊本幸司、岸和田昌之、大澤一郎、濱田賢司、水野修吾、櫻井洋至、田端正己、伊佐地秀司
  • Organizer: 日本肝胆膵外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-05-21
• [Presentation] 肝移植後長期にわたるカルシニューリン・インヒビターに及ぼすCYP3A5遺伝子多型の影響 (2009)
  • Author(s): 臼井正信、大倉康生、熊本幸司、岸和田昌之、大澤一郎、濱田賢司、水野修吾、櫻井洋至、田端正己、伊佐地秀司
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-04-08
• [Remarks] ホームページ
  • URL: http://web.me.com/shujiisaji1/
• [Remarks] 三重大学肝胆膵・移植外科