The IL20 Genetic Polymorphism Is Associated with Altered Clinical Outcome in Septic Shock.

• Project/Area Number: 15H02568
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Chiba University
• Principal Investigator: Nakada Taka-aki 千葉大学, 大学院医学研究院, 教授 (20375794)
• Co-Investigator(Kenkyū-buntansha): 安部 隆三 千葉大学, 医学部附属病院, 講師 (30375795) ; 関根 章博 千葉大学, 予防医学センター, 教授 (30425631) ; 織田 成人 千葉大学, 大学院医学研究院, 教授 (90204205)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥38,480,000 (Direct Cost: ¥29,600,000、Indirect Cost: ¥8,880,000); Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2016: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: IL-10 / IL-19 / IL-20 / IL-24 / 遺伝子多型 / SNPs / single nucleotide polymorphisms / 敗血症 / EXON / 救急 / 集中治療 / exon / 個別化医療

Outline of Final Research Achievements

We tested the hypothesis that SNPs in IL10, IL19, IL20, and IL24 of the IL10 family gene alter clinical outcome of septic shock. Patients with septic shock (n=1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n=981) were genotyped for IL20 rs2981573 A/G.
Patients with the G allele of IL20 rs2981573 had a significantly increased 28-day mortality compared to A allele in septic shock (adjusted HR 1.27; p=8.0×10-4). Patients with the GG genotype had more organ dysfunction (p<0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p<0.05). The cardiac surgical ICU patients with the GG genotype had an increased ICU stay (p=0.032). The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.

Academic Significance and Societal Importance of the Research Achievements

敗血症は依然致死率が高く，新規発見が必要な重要課題である．遺伝的要因の個人差である遺伝子多型が敗血症の転帰に影響を与えることが広く知られている．敗血症の転帰に影響を与える遺伝子多型を同定し，その情報に基づき個別化医療を行うことで敗血症の生存率が向上すると考えられる．

Research Products

• [Journal Article] Identification of a non-synonymous polymorphism in the SVEP1 gene associated with altered clinical outcomes in septic shock. (2015)
  • Author(s): Nakada TA, Russell JA, Boyd JH, Thair SA, Walley KR.
  • Journal Title: Crit Care Med. Volume: 43 Issue: 1 Pages: 101-108
  • DOI: 10.1097/ccm.0000000000000604
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] VPS13D gene variant is associated with altered IL-6 production and mortality in septic shock. (2015)
  • Author(s): Nakada TA, Boyd JH, Russell JA, Aguirre-Hern&aacute;ndez R, Wilkinson MD, Thair SA, Nakada E, McConechy MK, Fjell CD, Walley KR.
  • Journal Title: J Innate Immun. Volume: 7 Issue: 5 Pages: 545-543
  • DOI: 10.1159/000381265
  • Peer Reviewed / Int'l Joint Research
• [Presentation] nterleukin-10ファミリー遺伝子の一塩基多型と敗血症性ショック患者の転帰 (2017)
  • Author(s): 中田孝明
  • Organizer: 日本外科学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2017-04-27
• [Presentation] Interleukin-10ファミリー遺伝子の一塩基多型と敗血症性ショック患者の転帰との関連 (2017)
  • Author(s): 中田孝明
  • Organizer: 日本外科学会