Effect of autophagy-related polymorphism on inflammatory reaction of severe SIRS

• Project/Area Number: 23792070
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Tokyo Women's Medical University (2013); Chiba University (2011-2012)
• Principal Investigator: KIMURA TOMONORI 東京女子医科大学, 医学部, 医療練士研修生 (90598236)
• Research Collaborator: WATANABE Eizo 千葉大学, 大学院医学研究科, 准教授 (40375639) ; ODA Shigeto 千葉大学, 大学院医学研究科, 教授 (90204205)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 重症敗血症 / オートファジー / 遺伝子多型 / severe sepsis / IL-1ra VNTR / 重症感染症 / Autophagy / SIRS / 炎症性サイトカイン

Research Abstract

We examined the association between autophagy-related IRGM (human immunity-related GTPase) polymorphism and clinical course/outcome in patients with severe sepsis. We have set the 2 cohorts and lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers was performed for comparison of IRGM mRNA expression among different genotypes. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than that of the CC+CT genotype category in the severe sepsis group for both cohorts. Lipopolysaccharide challenge showed a significant suppression of IRGM mRNA expression in TT homozygotes compared with that of the CC+CT genotype category. The data suggest that IRGM(+313) SNP, an autophagy-related polymorphic locus, influences outcome in patients with severe sepsis, with the possible involvement of autophagy in sepsis exacerbation.

Research Products

• [Journal Article] Autophagy-Related IRGM polymorphism is associated with mortality of patients with severe sepsis (2014)
  • Author(s): Kimura T, Watanabe E, Sakamoto T, Takasu O, Ikeda T, Ikeda K, Kotani J, Kitamura N, Sadahiro T, Tateishi Y, Shinozaki K, Oda S
  • Journal Title: PLoS ONE Volume: 9
• [Journal Article] Autophagy-related IRGM polymorphism is associated with mortality of patients with severe sepsis (2014)
  • Author(s): Tomonori K, Watanabe E, Sakamoto T, Takasu O, Ikeda T, Ikeda K, Kotani J, Kitamura N, Sadahiro T, Tateishi Y, Shinozaki K, Oda S
  • Journal Title: PLoS ONE Volume: 9 Issue: 3 Pages: e91522-e91522
  • DOI: 10.1371/journal.pone.0091522
  • Peer Reviewed
• [Journal Article] 遺伝子多型に起因する免疫異常と重症敗血症 (2013)
  • Author(s): 渡邉栄三,織田成人,木村友則,中田孝明,大谷俊介,島田忠長,平澤博之
  • Journal Title: ICUとCCU Volume: 37 Pages: 585-592
• [Journal Article] 遺伝子多型に起因する免疫異常と重症敗血症 (2013)
  • Author(s): 渡邉栄三, 織田成人, 木村友則, 中田孝明, 大谷俊介, 島田忠長, 平澤博之
  • Journal Title: ICUとCCU Volume: 37 Pages: 585-92
• [Presentation] IRGM遺伝子多型がSevere Sepsis患者の転帰に与える影響 (2014)
  • Author(s): 木村友則,渡邉栄三,織田成人,坂本照夫,池田寿昭,池田一美,小谷穣治,北村伸哉,立石順久,篠崎広一郎
  • Organizer: 第41回日本集中治療医学会総会・学術集会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-02-28
• [Presentation] IRGM遺伝子多型がSevere Sepsis患者の転帰に与える影響 (2014)
  • Author(s): 木村友則, 渡邉栄三, 織田成人, 坂本照夫,池田寿昭, 池田一美, 小谷穣治, 北村伸哉, 立石順久, 篠崎広一郎
  • Organizer: 第41回日本集中治療医学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] An IRGM polymorphism (rs10065172) is associated with mortality of severe sepsis through the down-regulation of IRGM gene expression with LPS challenge (2013)
  • Author(s): Watanabe E, Kimura T, Teratani A, Sakamoto T, Ikeda T, Ikeda K, Kotani J, Kitamura N, Oda S
  • Organizer: The 11th World Federation of Societies of Intensive and Critical Care Congress 2013
  • Place of Presentation: Durban, South Africa
  • Year and Date: 2013-08-30
• [Presentation] Autophagyの重症敗血症における役割とその制御による臨床応用の可能性 (2013)
  • Author(s): 渡邉栄三,幡野雅彦,仲村将高,高橋和香,木村友則, Paul E Swanson,織田成人
  • Organizer: 第28回日本Shock学会総会2013
  • Place of Presentation: 北里大学薬学部コンベンションホール
  • Year and Date: 2013-05-18
• [Presentation] IRGM polymorphisms were associated with mortality and IL-6 blood levels of severely septic patients (2012)
  • Author(s): Watanabe E, Kimura T, Teratani A, Sakamoto T, Ikeda T, Ikeda K, Kotani J, Kitamura N, Oda S
  • Organizer: The 6th International Symposium on Autophagy 2012
  • Place of Presentation: Okinawa
  • Year and Date: 2012-10-29
• [Presentation] 敗血症性臓器障害におけるAutophagy-臨床および基礎医学的研究- (2012)
  • Author(s): 渡邉栄三,高橋和香,幡野雅彦,織田成人
  • Organizer: 第21回日本Cell Death学会学術集会2012
  • Place of Presentation: 名古屋大学医学部付属病院中央診療棟3階講堂
  • Year and Date: 2012-07-28
• [Presentation] sepsis患者の転帰およびサイトカイン発現におよぼすインターロイキン-1(IL-1)関連遺伝子多型の影響 (2012)
  • Author(s): 木村友則、他
  • Organizer: 第25回日本外科感染症学会総会学術集会
  • Place of Presentation: 千葉
• [Presentation] インターロイキン-1関連遺伝子多型の重症敗血症の予後およびサイトカイン産生能におよぼす影響 (2012)
  • Author(s): 木村 友則, 渡邉 栄三, 織田 成人, 貞広 智仁, 仲村 将高, 安部 隆三, 中田 孝明, 森田 泰正, 高井 信幸, 平澤 博之
  • Organizer: 第39回 日本集中治療医学会学術集会
  • Place of Presentation: 千葉