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ABOエンハンサーはADAMTS13の転写を活性化する-知られざる血栓症の機序-

Research Project

Project/Area Number 23K09758
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 58040:Forensics medicine-related
Research InstitutionGunma University

Principal Investigator

佐野 利恵  群馬大学, 大学院医学系研究科, 准教授 (70455955)

Co-Investigator(Kenkyū-buntansha) 早川 輝  群馬大学, 大学院医学系研究科, 講師 (90758575)
高橋 遥一郎  筑波大学, 医学医療系, 教授 (50640538)
福田 治紀  群馬大学, 大学院医学系研究科, 助教 (00977895)
窪 理英子  群馬大学, 医学部, 技術職員 (40747127)
Project Period (FY) 2023-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsABO遺伝子 / ABO式血液型 / ADAMTS13 / TAD
Outline of Research at the Start

予備実験及びゲノムアノテーションデータから、第9染色体長腕9q34.2にあるABO遺伝子とADAMTS13遺伝子がクロマチンループ構造により近接し,ABO遺伝子エンハンサー+22.6-kb siteがADAMTS13遺伝子の転写を活性化すると考えられる。本研究では,培養細胞やゲノム編集を用いたin vitro assay,病理組織切片を用いたin situ hybridization等からABO遺伝子とADAMTS13遺伝子の共同する転写調節機構を明らかにし,血栓症の病態解明を介して医療に貢献する。

Outline of Annual Research Achievements

血栓症の機序として止血因子von Willebrand factor (vWF)の特異的切断酵素であるA Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13)の機能低下が知られている。一方,静脈血栓症等の重症度とABO式血液型が関連することが明らかとなっているが,その機序は完全には解明されていない。申請者は,予備実験及びゲノムアノテーションデータから、第9染色体長腕9q34.2にあるABO遺伝子とADAMTS13遺伝子がクロマチンループ構造により近接し,ABO遺伝子エンハンサー+22.6-kb siteがADAMTS13遺伝子の転写を活性化すると考えた。本研究では,各種培養細胞について、ABO遺伝子発現の有無についてRT-qPCRにて予備的検討を行った。今後、レポーターアッセイを行い、ABOエンハンサーがADAMTS13遺伝子発現に及ぼす影響を検討する予定である。

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

法医鑑定業務の過多により、実験的検討が遅延している。

Strategy for Future Research Activity

これまでの予備的検討により、実験に用いる培養細胞の選別が可能となったことから、今後は実際に培養細胞を用いた試験管内実験を推進する。

Report

(1 results)
  • 2023 Research-status Report
  • Research Products

    (17 results)

All 2023

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] A novel genotyping method for rapid identification of the Le gene to select patients for diagnosis with CA19-9.2023

    • Author(s)
      Sano R, Yokobori T, Harimoto N, Saeki H, Kominato Y, Shirabe K, Yazawa S.
    • Journal Title

      Clin Chim Acta.

      Volume: 538 Pages: 181-188

    • DOI

      10.1016/j.cca.2022.11.006

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Post-traumatic cerebral infarction caused by thrombus in the middle cerebral artery2023

    • Author(s)
      Hayakawa Akira、Sano Rie、Takahashi Yoichiro、Fukuda Haruki、Okawa Takafumi、Kubo Rieko、Takei Hiroyuki、Komatsu Takakazu、Tokue Hiroyuki、Sawada Yusuke、Oshima Kiyohiro、Horioka Kie、Kominato Yoshihiko
    • Journal Title

      Journal of Forensic and Legal Medicine

      Volume: 93 Pages: 102474-102474

    • DOI

      10.1016/j.jflm.2022.102474

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypothermic death resulting from extreme freezing with characteristic postmortem computed tomography findings: A case report and review of the literature2023

    • Author(s)
      Tokue Hiroyuki、Sano Rie、Takahashi Yoichiro、Hayakawa Akira、Fukuda Haruki、Tokue Azusa、Kominato Yoshihiko、Tsushima Yoshito
    • Journal Title

      Radiology Case Reports

      Volume: 18 Issue: 4 Pages: 1423-1426

    • DOI

      10.1016/j.radcr.2023.01.007

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emergence of an erythroid cell-specific regulatory region in ABO intron 1 attributable to A- or B-antigen expression on erythrocytes in Hominoidea2023

    • Author(s)
      Sano Rie、Fukuda Haruki、Kubo Rieko、Oishi Takao、Miyabe-Nishiwaki Takako、Kaneko Akihisa、Masato Haruhisa、Takahashi Yoichiro、Hayakawa Akira、Yazawa Shin、Kominato Yoshihiko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 4947-4947

    • DOI

      10.1038/s41598-023-31961-6

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute subdural hematoma caused by rupture of a mycotic aneurysm due to meningitis associated with infectious endocarditis: comparison of autopsy findings with postmortem computed tomography2023

    • Author(s)
      Fukuda Haruki、Hayakawa Akira、Takahashi Yoichiro、Komatsu Yuka、Kawamura Miki、Kubo Rieko、Tokue Hiroyuki、Kominato Yoshihiko、Sano Rie
    • Journal Title

      Forensic Science, Medicine and Pathology

      Volume: - Issue: 2 Pages: 0-0

    • DOI

      10.1007/s12024-023-00640-3

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Corrigendum to “Investigation of the applicability of virtual gastroscopy based on postmortem computed tomography to detect changes in the stomach, along with reports of three rare cases” [Legal Med. 52 (2021) 101898]2023

    • Author(s)
      Fukuda Haruki、Sano Rie、Hayakawa Akira、Takahashi Yoichiro、Okawa Takafumi、Kubo Rieko、Takei Hiroyuki、Awata Sachiko、Tokue Hiroyuki、Akuzawa Hisashi、Yuasa Masahiro、Kominato Yoshihiko
    • Journal Title

      Legal Medicine

      Volume: 63 Pages: 102219-102219

    • DOI

      10.1016/j.legalmed.2023.102219

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Usefulness of virtual reassembly of the skull and spine in cases of fragmentation due to high-energy trauma: A feasibility study2023

    • Author(s)
      Fukuda Haruki、Hayakawa Akira、Tokue Hiroyuki、Takahashi Yoichiro、Kominato Yoshihiko、Sano Rie
    • Journal Title

      Legal Medicine

      Volume: 64 Pages: 102281-102281

    • DOI

      10.1016/j.legalmed.2023.102281

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Postmortem genetic analysis of 17 sudden cardiac deaths identified nonsense and frameshift variants in two cases of arrhythmogenic cardiomyopathy2023

    • Author(s)
      Takahashi Yoichiro、Fukuda Haruki、Hayakawa Akira、Sano Rie、Kubo Rieko、Kawabata-Iwakawa Reika、Nakajima Tadashi、Ishige Takashi、Tokue Hiroyuki、Asano Kazuya、Seki Tomohiro、Hsiao Yi-Yang、Ishizawa Fujio、Takei Hiroyuki、Kominato Yoshihiko
    • Journal Title

      International Journal of Legal Medicine

      Volume: 137 Issue: 6 Pages: 1927-1937

    • DOI

      10.1007/s00414-023-03037-7

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Presentation] Usefulness of virtual reassembly of skull or spine in cases of fragmentation due to high-energy trauma or bone separation through postmortem changes.2023

    • Author(s)
      H. Fukuda, A. Hayakawa, R. Kubo, H. Tokue, Y. Kominato, R. Sano.
    • Organizer
      The 23rd Triennial Meeting of International Association of Forensic Sciences (IAFS).
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] Usefulness of virtual reassembly of skull or spine in cases of fragmentation due to high-energy trauma or bone separation through postmortem changes. 12th Annual Meeting of the International Society for Forensic Radiology and Imaging (ISFRI).2023

    • Author(s)
      H. Fukuda, A. Hayakawa, R. Kubo, H. Tokue, Y. Kominato, R. Sano.
    • Organizer
      12th Annual Meeting of the International Society for Forensic Radiology and Imaging (ISFRI).
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] Virtual reassembly of the skull and spine in fragmentation due to trauma or postmortem changes.2023

    • Author(s)
      福田治紀, 早川 輝, 高橋遥一郎, 佐野利恵, 窪理英子, 徳江浩之, 小湊慶彦.
    • Organizer
      第107次日本法医学会学術全国集会.
    • Related Report
      2023 Research-status Report
  • [Presentation] 剖検及び死後CTの所見の比較-感染性脳動脈瘤破裂に基づく急性硬膜下血腫の一事例を通して-.2023

    • Author(s)
      福田治紀, 早川輝, 高橋遥一郎, 佐野利恵, 窪理英子, 徳江浩之, 小湊慶彦.
    • Organizer
      第107次日本法医学会学術全国集会.
    • Related Report
      2023 Research-status Report
  • [Presentation] 中大脳動脈内膜損傷に惹起された外傷後脳梗塞の一剖検例.2023

    • Author(s)
      早川輝,佐野利恵,高橋遥一郎,福田治紀,窪理英子,徳江浩之,小湊慶彦.
    • Organizer
      第107次日本法医学会学術全国集会.
    • Related Report
      2023 Research-status Report
  • [Presentation] てんかん関連突然死例の家族を含めた遺伝子解析.2023

    • Author(s)
      佐野利恵,早川輝,高橋遥一郎,福田治紀,窪理英子,小湊慶彦.
    • Organizer
      第107次日本法医学会学術全国集会.
    • Related Report
      2023 Research-status Report
  • [Presentation] 外性器への特徴的な異物の装着・挿入を認めた覚せい剤乱用者の一剖検例.2023

    • Author(s)
      福田治紀, 早川輝, 佐野利恵, 窪理英子, 徳江浩之, 小湊慶彦.
    • Organizer
      第92回日本法医学会学術関東地方集会.
    • Related Report
      2023 Research-status Report
  • [Presentation] 剖検及び死後CTの所見の比較-感染性脳動脈瘤破裂に基づく急性硬膜下血腫の一事例を通して-.2023

    • Author(s)
      福田治紀、早川輝、高橋遥一郎、佐野利恵、窪理英子、徳江浩之、小湊慶彦.
    • Organizer
      第23回法医画像勉強会.
    • Related Report
      2023 Research-status Report
  • [Presentation] ABO式血液型の遺伝学 (教育講演)2023

    • Author(s)
      佐野利恵
    • Organizer
      第107次日本法医学会学術全国集会
    • Related Report
      2023 Research-status Report
    • Invited

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Published: 2023-04-13   Modified: 2024-12-25  

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