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Assessment of epigenome changes in fetal chemical exposure

Research Project

Project/Area Number 20K21707
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 58:Society medicine, nursing, and related fields
Research InstitutionUniversity of Yamanashi

Principal Investigator

Miyake Kunio  山梨大学, 大学院総合研究部, 准教授 (60550712)

Co-Investigator(Kenkyū-buntansha) 幸田 尚  山梨大学, 大学院総合研究部, 教授 (60211893)
宮下 ちひろ  北海道大学, 環境健康科学研究教育センター, 特任教授 (70632389)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywordsエピジェネティクス / 出生コホート / DNAメチル化 / ADHD / DOHaD / DNAヒドロキシメチル化 / 喫煙曝露 / 次世代シークエンサー / 胎児期 / エピゲノム / 化学物質曝露 / DNA修飾
Outline of Research at the Start

近年、胎児期の化学物質曝露と成長後の疾患リスクを結ぶエピゲノム疫学研究が盛んに行われ、これまでは“エピゲノム(DNA化学修飾)=DNAメチル化”として変化する遺伝子が報告されているが、他のDNA化学修飾であるヒドロキシメチル化については全く考慮されていない。これまでの解析方法ではヒドロキシメチル化修飾されていた場合もメチル化として判定されしまうため、誤ったDNA修飾情報を基盤に解析が進められている可能性が高い。本研究はDNAの非メチル化・メチル化・ハイドロキシメチル化を同時に高感度で解析できるエニグマ法を用いることで化学物質曝露による真のDNA化学修飾変化を明らかにすることを目的とする。

Outline of Final Research Achievements

The concept of Developmental Origins of Health and Disease (DOHaD) has been established that various environmental factors in the fetal period and infancy affect future health and the risk of developing diseases. TThe purpose of this study was to analyze DNA methylation and hydroxymethylation changes affected by cigarette smoke exposure and to clarify their involvement in the development of children. As a result, there were significant changes in cord blood DNA with maternal smoking exposure during pregnancy and DNA methylation of the five genes, but no association with DNA hydroxymethylation.

Academic Significance and Societal Importance of the Research Achievements

胎児期や乳幼児期の劣悪な環境(低栄養、ストレス、喫煙曝露など)は成長後のさまざまな疾患(糖尿病、アレルギー、神経発達障害など)のリスクを増加させる。本研究では、妊婦中の母親の喫煙はDNAメチル化を変化させ、子供の神経発達障害リスクの増加と関与することがわかった。したがって妊娠初期からの環境は子どもの将来の疾患リスクに影響することを科学的エビデンスに基づいて証明できたことは学術的、社会的意義は大きい。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (25 results)

All 2022 2021 2020 Other

All Journal Article (19 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 19 results,  Open Access: 17 results) Presentation (4 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Mother’s iodine exposure and infants’ hypothyroidism: the Japan Environment and Children’s Study (JECS)2022

    • Author(s)
      Yokomichi Hiroshi、Mochizuki Mie、Kojima Reiji、Horiuchi Sayaka、Ooka Tadao、Akiyama Yuka、Miyake Kunio、Kushima Megumi、Otawa Sanae、Shinohara Ryoji、Yamagata Zentaro
    • Journal Title

      Endocrine Journal

      Volume: 69 Issue: 1 Pages: 9-21

    • DOI

      10.1507/endocrj.EJ21-0168

    • NAID

      130008145295

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of allele-specific methylation of the <i>ASNS</i> gene with asparaginase sensitivity and prognosis in T-ALL2022

    • Author(s)
      Akahane Koshi、Kimura Shunsuke、Miyake Kunio、Watanabe Atsushi、Kagami Keiko、Yoshimura Kentaro、Shinohara Tamao、Harama Daisuke、Kasai Shin、Goi Kumiko、Kawai Tomoko、Hata Kenichiro、Kiyokawa Nobutaka、Koh Katsuyoshi、他7名
    • Journal Title

      Blood Advances

      Volume: 6 Issue: 1 Pages: 212-224

    • DOI

      10.1182/bloodadvances.2021004271

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High Incidence of Atopic Dermatitis among Children Whose Fathers Work in Primary Industry: The Japan Environment and Children’s Study (JECS)2022

    • Author(s)
      Yokomichi Hiroshi、Mochizuki Mie、Kojima Reiji、Horiuchi Sayaka、Ooka Tadao、Akiyama Yuka、Miyake Kunio、Kushima Megumi、Otawa Sanae、Shinohara Ryoji、Yamagata Zentaro、on behalf of the Japan Environment and Children’s Study Group
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 19 Issue: 3 Pages: 1761-1761

    • DOI

      10.3390/ijerph19031761

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA methylation of GFI1 as a mediator of the association between prenatal smoking exposure and ADHD symptoms at 6 years: the Hokkaido Study on Environment and Children’s Health2021

    • Author(s)
      Miyake Kunio、Miyashita Chihiro、Ikeda-Araki Atsuko、Miura Ryu、Itoh Sachiko、Yamazaki Keiko、Kobayashi Sumitaka、Masuda Hideyuki、Ooka Tadao、Yamagata Zentaro、Kishi Reiko
    • Journal Title

      Clinical Epigenetics

      Volume: 13 Issue: 1 Pages: 74-74

    • DOI

      10.1186/s13148-021-01063-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of prenatal exposure to phthalates on epigenome-wide DNA methylations in cord blood and implications for fetal growth: The Hokkaido Study on Environment and Children's Health2021

    • Author(s)
      Miura Ryu、Ikeda-Araki Atsuko、Ishihara Toru、Miyake Kunio、Miyashita Chihiro、Nakajima Tamie、Kobayashi Sumitaka、Ishizuka Mayumi、Kubota Takeo、Kishi Reiko
    • Journal Title

      Science of The Total Environment

      Volume: 783 Pages: 147035-147035

    • DOI

      10.1016/j.scitotenv.2021.147035

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between gestational hair dye use and allergies at 3 years old: the Japan environment and Children's study2021

    • Author(s)
      Kojima Reiji、Shinohara Ryoji、Horiuchi Sayaka、Otawa Sanae、Yokomichi Hiroshi、Akiyama Yuka、Ooka Tadao、Miyake Kunio、Yamagata Zentaro
    • Journal Title

      Environmental Research

      Volume: 201 Pages: 111530-111530

    • DOI

      10.1016/j.envres.2021.111530

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic Modification of Death Receptor Genes for TRAIL and TRAIL Resistance in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia2021

    • Author(s)
      Watanabe Atsushi、Miyake Kunio、Akahane Koshi、Goi Kumiko、Kagami Keiko、Yagita Hideo、Inukai Takeshi
    • Journal Title

      Genes

      Volume: 12 Issue: 6 Pages: 864-864

    • DOI

      10.3390/genes12060864

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of the incidence of atopic dermatitis until 3 years old with birth month and with sunshine duration and humidity in the first 6 months of life: Japan Environment and Children’s Study2021

    • Author(s)
      Yokomichi Hiroshi、Mochizuki Mie、Tsuchida Akiko、Kojima Reiji、Horiuchi Sayaka、Ooka Tadao、Akiyama Yuka、Miyake Kunio、Otawa Sanae、Shinohara Ryoji、Inadera Hidekuni、Yamagata Zentaro
    • Journal Title

      BMJ Open

      Volume: 11 Issue: 7 Pages: 1-6

    • DOI

      10.1136/bmjopen-2020-047226

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening of frequent variants associated with congenital hypothyroidism: a comparison with next generation sequencing2021

    • Author(s)
      Watanabe Daisuke、Yagasaki Hideaki、Narusawa Hiromune、Saito Tomohiro、Mitsui Yumiko、Miyake Kunio、Ohta Masanori、Inukai Takeshi
    • Journal Title

      Endocrine Journal

      Volume: 68 Issue: 12 Pages: 1411-1419

    • DOI

      10.1507/endocrj.EJ21-0353

    • NAID

      130008136503

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gestational body weight gain and risk of low birth weight or macrosomia in women of Japan: a nationwide cohort study2021

    • Author(s)
      Uchinuma Hiroyuki、Tsuchiya Kyoichiro、Sekine Tetsuo、Horiuchi Sayaka、Kushima Megumi、Otawa Sanae、Yokomichi Hiroshi、Miyake Kunio、Akiyama Yuka、Ooka Tadao、Kojima Reiji、Shinohara Ryoji、Hirata Shuji、Yamagata Zentaro; Japan Environment and Children’s Study Group
    • Journal Title

      International Journal of Obesity

      Volume: 45 Issue: 12 Pages: 2666-2674

    • DOI

      10.1038/s41366-021-00947-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between Household Income and Allergy Development in Children: The Japan Environment and Children’s Study2021

    • Author(s)
      Kojima Reiji、Shinohara Ryoji、Kushima Megumi、Horiuchi Sayaka、Otawa Sanae、Yokomichi Hiroshi、Akiyama Yuka、Ooka Tadao、Miyake Kunio、Yamagata Zentaro、the Japan Environment and Children’s Study Group
    • Journal Title

      International Archives of Allergy and Immunology

      Volume: 183 Issue: 2 Pages: 201-209

    • DOI

      10.1159/000519153

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elective cesarean delivery at term and its effects on respiratory distress at birth in Japan: The Japan Environment and Children's Study2021

    • Author(s)
      Horiuchi Sayaka、Shinohara Ryoji、Otawa Sanae、Kushima Megumi、Akiyama Yuka、Ooka Tadao、Kojima Reiji、Yokomichi Hiroshi、Miyake Kunio、Yamagata Zentaro、The Japan Environment and Children's Study Group
    • Journal Title

      Health Science Reports

      Volume: 4 Issue: 4

    • DOI

      10.1002/hsr2.421

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between Maternal Exposure to Chemicals during Pregnancy and the Risk of Foetal Death: The Japan Environment and Children’s Study2021

    • Author(s)
      Ooka Tadao、Horiuchi Sayaka、Shinohara Ryoji、Kojima Reiji、Akiyama Yuka、Miyake Kunio、Otawa Sanae、Yokomichi Hiroshi、Yamagata Zentaro、on behalf of the Japan Environment and Children’s Study Group
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 22 Pages: 11748-11748

    • DOI

      10.3390/ijerph182211748

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of Maternal Active and Secondhand Smoking during Pregnancy on Childhood Obesity at 3 Years of Age: A Nested Case?Control Study from the Japan Environment and Children’s Study (JECS)2021

    • Author(s)
      Horiuchi Sayaka、Shinohara Ryoji、Otawa Sanae、Kushima Megumi、Akiyama Yuka、Ooka Tadao、Kojima Reiji、Yokomichi Hiroshi、Miyake Kunio、Hirai Hiroyuki、Hashimoto Koichi、Shimabukuro Michio、Yamagata Zentaro、Japan Environment and Children’s Study Group
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 23 Pages: 12506-12506

    • DOI

      10.3390/ijerph182312506

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factors of parental COVID-19 vaccine hesitancy: A cross sectional study in Japan2021

    • Author(s)
      Horiuchi Sayaka、Sakamoto Haruka、Abe Sarah K.、Shinohara Ryoji、Kushima Megumi、Otawa Sanae、Yui Hideki、Akiyama Yuka、Ooka Tadao、Kojima Reiji、Yokomichi Hiroshi、Miyake Kunio、Mizutani Takashi、Yamagata Zentaro
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 12 Pages: e0261121-e0261121

    • DOI

      10.1371/journal.pone.0261121

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between preterm birth and maternal allergy considering IgE level2021

    • Author(s)
      Kojima Reiji、Yokomichi Hiroshi、Akiyama Yuka、Ooka Tadao、Miyake Kunio、Horiuchi Sayaka、Shinohara Ryoji、Yamagata Zentaro、Japan Environment, Children's Study Group
    • Journal Title

      Pediatrics International

      Volume: 63 Issue: 9 Pages: 1026-1032

    • DOI

      10.1111/ped.14635

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL2020

    • Author(s)
      Atsushi Watanabe, Kunio Miyake, Jessica Nordlund, Ann-Christine Syvanen, Louise van der Weyden, Hiroaki Honda, Norimasa Yamasaki, Akiko Nagamachi, Toshiya Inaba, Tomokatsu Ikawa, Kevin Y Urayama, Nobutaka Kiyokawa, Akira Ohara, Shunsuke Kimura, Yasuo Kubota, Junko Takita, Hiroaki Goto, Kimiyoshi Sakaguchi, et al.
    • Journal Title

      Blood

      Volume: 136 Issue: 20 Pages: 2319-2333

    • DOI

      10.1182/blood.2019004090

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of MGMT methylation status using high-performance liquid chromatography in newly diagnosed glioblastoma2020

    • Author(s)
      Hanihara M, Miyake K, Watanabe A, Yamada Y, Oishi N, Kawataki T, Inukai T, Kondo T, Kinouchi H.
    • Journal Title

      Clin Epigenetics

      Volume: 12(1) Issue: 1 Pages: 174-174

    • DOI

      10.1186/s13148-020-00968-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] LPCAT2 Methylation, a Novel Biomarker for the Severity of Cedar Pollen Allergic Rhinitis in Japan2020

    • Author(s)
      Watanabe H, Miyake K, Matsuoka T, Kojima R, Sakurai D, Masuyama K, Yamagata Z.
    • Journal Title

      Am J Rhinol Allergy.

      Volume: - Issue: 5 Pages: 631-639

    • DOI

      10.1177/1945892420983646

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] STAT3活性化変異を有する節外性NK/T細胞リンパ腫・鼻型はCD30を高発現する2021

    • Author(s)
      大石 直輝,佐藤 啓,川島 一郎,瀬川 高弘,三宅 邦夫, 望月 邦夫,桐戸 敬太,近藤 哲夫
    • Organizer
      第61回日本リンパ網内系学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞を用いた発生初期からのタバコ煙曝露による神経細胞分化への影響2021

    • Author(s)
      三宅邦夫
    • Organizer
      日本環境変異原ゲノム学会第50回記念大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 白血病細胞のASNS遺伝子のメチル化解析におけるHPLC法の有用性2020

    • Author(s)
      渡邊 敦, 三宅 邦夫, 篠原 珠緒, 原間 大輔, 笠井 慎, 村上 寧, 赤羽弘資, 合井 久美子,山田 有理子, 砂村 栄一郎, 與谷 卓也, 犬飼 岳史
    • Organizer
      第123回日本小児科学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 膠芽腫におけるMGMT遺伝子メチル化の新規解析法 -HPLC法-2020

    • Author(s)
      埴原 光人、川瀧 智之、荻原 雅和、三宅 邦夫、渡邊 敦、大石 直輝、山田有理子、犬飼 岳史、木内 博之
    • Organizer
      日本脳神経外科学会第79回学術集会
    • Related Report
      2020 Research-status Report
  • [Remarks] 山梨大学大学院総合研究部医学域社会医学講座ホームページ

    • URL

      https://www.med.yamanashi.ac.jp/social/heal0sci/

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Patent(Industrial Property Rights)] 胃がん細胞の増殖抑制剤、胃がんの腫瘍形成抑制剤、胃がんを治療するための医薬、及び薬効予測方法2021

    • Inventor(s)
      犬飼 岳史、渡邊 敦、赤羽 弘資、三宅 邦夫
    • Industrial Property Rights Holder
      国立大学法人山梨大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-116120
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2020-08-03   Modified: 2023-01-30  

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