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Investigation of effects of environmental pollutants on metabolisms and endocrine with novel chemical analyses and genetic analyses

Research Project

Project/Area Number 20H03930
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research InstitutionKyoto University

Principal Investigator

Harada Kouji  京都大学, 医学研究科, 准教授 (80452340)

Co-Investigator(Kenkyū-buntansha) 原田 真理子  京都大学, 医学研究科, 研究員 (10553399)
小林 果  三重大学, 医学系研究科, 講師 (70542091)
藤井 由希子  第一薬科大学, 薬学部, 准教授 (80733542)
藤谷 倫子  京都大学, 医学研究科, 研究員 (90836412)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords環境汚染物質 / 代謝遺伝子 / SNPs / 個人差 / ランダムメンデル化 / メンデルランダム化 / 内分泌 / 代謝 / 遺伝子
Outline of Research at the Start

有機フッ素化合物、有機臭素化合物などの残留性有機汚染物質、フタル酸エステル、有機リン系農薬・難燃剤などの短半減期汚染物質の代謝に関わる遺伝子多型を日本人集団において明らかにし、操作変数とし、それに対して、これまでに関連が認められた代謝・ホルモン関連アウトカムとの因果関係を検討する。またアウトカムとなる代謝・ホルモンレベルについて、新規化学分析法により測定精度を高めることにより、関連の検出を確かなものとする。

Outline of Final Research Achievements

The purpose of this study was to analyze the association between serum DDT and PCB concentrations and CYP2B6 and CYP1 family polymorphisms in a Japanese population and to determine the genetic effects on organochlorine concentrations. In addition, persistent organic pollutants were also examined and their associations with other CYP2 family polymorphisms were evaluated. Serum DDT and DDE concentrations were significantly lower in CYP2B6*4 carriers and higher in CYP2B6*6 carriers compared to the major haplotype CYP2B6*1. CYP1A1*1/*2B was associated with lower p,p'-DDT levels compared to the major genotype, CYP1A1*1/*1 (p=0.0086).

Academic Significance and Societal Importance of the Research Achievements

多くの化学物質の健康リスク研究において、動物実験による初期評価から疫学研究により詳細に評価する段階になっている。一方で、疫学研究において観察研究の限界として、種々のバイアス、交絡要因により、真の因果関係を評価することは困難であり、エビデンスレベルの高い研究が望まれている。本課題では残留性有機汚染物質の代謝に関わる遺伝子多型を日本人集団において明らかにできた。これを操作変数とし、これまでに関連が認められた疾患アウトカムとの因果関係を検討する基盤を提供することになる。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (14 results)

All 2023 2022 2021

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (4 results) Funded Workshop (1 results)

  • [Journal Article] Association between urinary zinc excretion and isoflavone-metabolizing enterotypes among Japanese females: a cross-sectional study2023

    • Author(s)
      Fujitani Tomoko、Lyu Zhaoqing、Sassa Mariko Harada、Harada Kouji H.
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: 28 Issue: 0 Pages: 63-63

    • DOI

      10.1265/ehpm.23-00148

    • ISSN
      1342-078X, 1347-4715
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasma eicosapentaenoic acid, a biomarker of fish consumption, is associated with perfluoroalkyl carboxylic acid exposure in residents of Kyoto, Japan: a cross-sectional study2023

    • Author(s)
      Soleman Sani Rachman、Li Meng、Fujitani Tomoko、Harada Kouji H.
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: 28 Issue: 0 Pages: 38-38

    • DOI

      10.1265/ehpm.22-00302

    • ISSN
      1342-078X, 1347-4715
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between lignan polyphenol bioavailability and enterotypes of isoflavone metabolism: A cross-sectional analysis2023

    • Author(s)
      Fujitani Tomoko、Harada Sassa Mariko、Lyu Zhaoqing、Fujii Yukiko、Harada Kouji H.
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 12 Pages: e0295185-e0295185

    • DOI

      10.1371/journal.pone.0295185

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profiles and determinants of dicofol, endosulfans, mirex, and toxaphenes in breast milk samples from 10 prefectures in Japan2023

    • Author(s)
      Fujii Yukiko、Harada Kouji H.、Ito Yoshiko、Yoshitake Miho、Matsunobu Chiharu、Kato Yoshihisa、Ohta Chiho、Koga Nobuyuki、Kimura Osamu、Endo Tetsuya、Koizumi Akio、Haraguchi Koichi
    • Journal Title

      Chemosphere

      Volume: 311 Pages: 137002-137002

    • DOI

      10.1016/j.chemosphere.2022.137002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative detection of organic mercury in whole blood using derivatization and gas chromatographynegative chemical ionization-mass spectrometry2023

    • Author(s)
      Lyu Zhaoqing、Soleman Sani Rachman、Li Meng、Harada Kouji H.
    • Journal Title

      Journal of Environmental Exposure Assessment

      Volume: 2 Issue: 2 Pages: 1-1

    • DOI

      10.20517/jeea.2022.26

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chlorinated persistent organic pollutants in human breast milk in the Miyagi Prefecture disaster-affected area 1 year after the Great East Japan Earthquake of 20112023

    • Author(s)
      Choi Jungmi、Fujii Yukiko、Lyu Zhaoqing、Kobayashi Hatasu、Fujitani Tomoko、Harada Kouji H.
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: 28 Issue: 0 Pages: 27-27

    • DOI

      10.1265/ehpm.22-00260

    • ISSN
      1342-078X, 1347-4715
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Underestimated bisphenol exposures: Letter to the editor on “Monitoring of bisphenol A and bisphenol S in thermal paper receipts from the Italian market and estimated transdermal human intake: A pilot study”2022

    • Author(s)
      Fujitani Tomoko、Harada Kouji H.
    • Journal Title

      Science of The Total Environment

      Volume: 847 Pages: 157589-157589

    • DOI

      10.1016/j.scitotenv.2022.157589

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comment on “Maternal Perfluoroalkyl Substances, Thyroid Hormones, and <i>DIO</i> Genes: A Spanish Cross-sectional Study”: Predictability of Multiple Imputations for Large Amounts of Missing Data2022

    • Author(s)
      Kobayashi Sumitaka、Harada Kouji H.
    • Journal Title

      Environmental Science &amp; Technology

      Volume: 56 Issue: 8 Pages: 5276-5277

    • DOI

      10.1021/acs.est.1c08598

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comment on “Novel Perfluoroalkyl Ether Carboxylic Acids (PFECAs) and Sulfonic Acids (PFESAs)”: Overlooked Interactions with Perfluorooctanoic Acid2021

    • Author(s)
      Lyu Zhaoqing、Michikawa Takehiro、Harada Kouji H.
    • Journal Title

      Environmental Science &amp; Technology

      Volume: 55 Issue: 11 Pages: 7755-7756

    • DOI

      10.1021/acs.est.1c01945

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 日本人女性のDDT血中濃度における薬物代謝酵素CYP2B6遺伝子多型の影響2023

    • Author(s)
      藤本嵐、原田浩二、小林果、伊藤弘明、藤井由希子、山地太樹、春日好雄、津金昌一郎、岩崎 基
    • Organizer
      第93回日本衛生学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] PFOS異性体がGC-MSおよびLC-MS/MSによる血中濃度分析に与える影響2022

    • Author(s)
      Soleman Sani Rachman、呂 兆卿、 Ang Sea Meng Jeremy、李 萌、岡田 拓也、原田 浩二
    • Organizer
      第92回日本衛生学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 日本人女性のビスフェノール類の曝露の経年的推移の解析とリスク評価2022

    • Author(s)
      呂 兆卿、原田 浩二
    • Organizer
      第92回日本衛生学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 有機フッ素化合物と白血球DNAメチル化レベルの関連: 主成分回帰分析2022

    • Author(s)
      伊藤 弘明、原田 浩二、春日 好雄、横山 和仁、 吉田 輝彦、津金 昌一郎、岩崎 基
    • Organizer
      第92回日本衛生学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Funded Workshop] PFAS and AFFF contamination: chemical identification, source identification, and environmental health2021

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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