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Development of a biomarker for clarifying the antemortem experiences using DNA methylation of the NR3C1 promoter region in brains from pediatric victims of physical abuse

Research Project

Project/Area Number 16K15399
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Legal medicine
Research InstitutionGunma University

Principal Investigator

Kominato Yoshihiko  群馬大学, 大学院医学系研究科, 教授 (30205512)

Co-Investigator(Kenkyū-buntansha) 高橋 遥一郎  群馬大学, 大学院医学系研究科, 助教 (50640538)
佐野 利恵  群馬大学, 大学院医学系研究科, 准教授 (70455955)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords子どもの虐待 / 神経細胞 / DNAメチル化 / グルココルチコイド受容体遺伝子 / こどもの虐待 / 小児虐待 / 頭部外傷
Outline of Final Research Achievements

Diagnostic confirmation of child abuse at autopsy is a critical task for forensic pathologists. In such cases, retrieval of information on the antemortem experiences of deceased infants is crucial. Early life stress (ELS) has been suggested to cause epigenetic changes to genes in the brain, such as the Nuclear Receptor Subfamily 3, Group C, Member 1 gene (NR3C1). Conversely, evaluation of the epigenetic status in the postmortem brain might provide clues to the antemortem ELS experience. We examined DNA methylation of the 1F promoter region of NR3C1 in the postmortem brains of eight children including four ELS cases. As a result, DNA methylation was evident in ELS cases due to severe physical abuse. Epigenetic status may have potential application as a biomarker for clarifying the antemortem experiences of deceased.

Academic Significance and Societal Importance of the Research Achievements

子どもの虐待には身体的な障害の他に子どもの脳発達に悪影響を及ぼすことが明らかとなってきた。また、動物実験やヒトにおける研究から、早期の有害なライフストレスが脳の神経細胞にDNAメチル化を引き起こすことが示されてきた。我々は法医解剖事例の脳を用いて虐待と神経細胞の核受容体遺伝子プロモーターのDNAメチル化の関係を調べ、頭部外傷を伴う虐待例ではDNAメチル化の増加を明らかにした。神経細胞のDNAメチル化という後天性変化が生前の精神的ストレスのバイオマーカーになる可能性が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Use of postmortem computed tomography to retrieve small metal fragments derived from a weapon in the bodies of victims in two homicide cases2018

    • Author(s)
      Sano Rie、Takahashi Yoichiro、Hayakawa Akira、Murayama Masayuki、Kubo Rieko、Hirasawa Satoshi、Tokue Hiroyuki、Shimada Takehiro、Awata Sachiko、Takei Hiroyuki、Yuasa Masahiro、Uetake Shinji、Akuzawa Hisashi、Kominato Yoshihiko
    • Journal Title

      Legal Medicine

      Volume: 32 Pages: 87-89

    • DOI

      10.1016/j.legalmed.2018.03.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postmortem computed tomography evaluation of fatal gas embolism due to connection of an intravenous cannula to an oxygen supply.2017

    • Author(s)
      Takahashi Y, Sano R, Yasuda A, Kuboya E, Takahashi K, Kubo R, Kominato Y, Takei H, Kobayashi S, Shimada T, Awata S, Tokue H, Hirasawa S
    • Journal Title

      Leg Med

      Volume: 27 Pages: 1-4

    • DOI

      10.1016/j.legalmed.2017.11.005

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histone deacetylase inhibitor suppresses the expression of ABO in vitro, leading to reduced amount of ABO antigens on the surface of the epithelial cell2017

    • Author(s)
      Takahashi Y, Kubo R, Sano R, Nakajima T, Takahashi K, Kobayashi M, Kominato Y
    • Journal Title

      Transfusion

      Volume: 印刷中 Issue: 3 Pages: 554-562

    • DOI

      10.1111/trf.13958

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sequence analysis of ABO and its homologues is valid for species identification.2017

    • Author(s)
      Sano R, Fukuda H, Takahashi Y, Takahashi K, Kubo R, Kobayashi M, Fujihara J, Takeshita H, Kominato Y.
    • Journal Title

      Transfus Med

      Volume: 27 Issue: 6 Pages: 428-436

    • DOI

      10.1111/tme.12455

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of sudden unexpected infant death involving a homozygotic twin with the thermolabile CPT2 variant, accompanied by rotavirus infection and treatment with an antibiotic containing pivalic acid2016

    • Author(s)
      Takahashi Y, Sano R, Kominato Y, Kubo R, Takahashi K, Nakajima T, Takeshita H, Ishige T
    • Journal Title

      Legal medicine

      Volume: 22 Pages: 13-17

    • DOI

      10.1016/j.legalmed.2016.07.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] A3, B3型におけるABO遺伝子プロモーターの一塩基置換はCTCFの結合を減弱させる.2018

    • Author(s)
      佐野利恵, 高橋遥一郎, 伊佐和美, 常山初江, 小笠原健一, 横濱章彦, 小湊慶彦.
    • Organizer
      第66回日本輸血・細胞治療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 死後CT検査は凶器に由来する微小な金属片の同定および回収に有用である2018

    • Author(s)
      佐野利恵, 早川輝, 高橋遥一郎, 小湊慶彦.
    • Organizer
      第87回日本法医学会学術関東地方集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A3, B3型におけるABO遺伝子プロモーターの一塩基置換はCTCFの結合を減弱させる.2018

    • Author(s)
      佐野利恵, 高橋遥一郎, 窪理英子, 早川輝, 藤原純子, 竹下治男, 小湊慶彦
    • Organizer
      日本DNA多型学会第27回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Reduction of CTCF binding to the ABO promoter by nucleotide substitutions found in individuals with phenotypes A3 and B2018

    • Author(s)
      Sano R, Kubo R, TakahashiT T, Takeshita H, Kominato Y.
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Usefulness of coronary postmortem computed tomography angiography to detect lesions in the coronary artery and myocardium in cases of sudden death.2018

    • Author(s)
      Sano R, Takahashi Y, Kimura-Kataoka K, Takeshita H, Kominato Y
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 法医分子病理学的解析の実際-脂肪酸代謝異常2症例の提示と, 被虐待児への応用可能性について2017

    • Author(s)
      高橋遥一郎
    • Organizer
      第101次日本法医学会学術全国集会
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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