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Elucidation of mechanisms of metabolic disorder-associated genes by the integration of genomic and non-genomic approaches

Research Project

Project/Area Number 26290067
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Medical genome science
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Kato Norihiro  国立研究開発法人国立国際医療研究センター, その他部局等, その他 (80293934)

Co-Investigator(Kenkyū-buntansha) 並河 徹  島根大学, 医学部, 教授 (50180534)
Co-Investigator(Renkei-kenkyūsha) OKAMURA TADASHI  国立国際医療研究センター, 研究所, 室長 (00333790)
Research Collaborator TAKEUCHI FUMIHIKO  国立国際医療研究センター, 研究所, 室長
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords疾患モデル生物ゲノム / 遺伝子 / トランスクリプトーム / ゲノム / エピゲノム / マイクロアレイ / mRNA
Outline of Final Research Achievements

To narrow down the possible list of causative genes at loci or chromosomal regions, where genetic associations are detected through exploratory analyses such as genome-wide association study (GWAS) and to further elucidate the biological mechanisms of mRNA expression changes by such causative genes, we have addressed three principal themes in the case of metabolic disorders as follows. First, we have performed fine mapping of loci, which are found to be associated with metabolic disorders phenotypes in the inbred rats, thereby narrowing down the list of causative genes. Second, we have investigated impacts of epigenomic changes, in particular, DNA methylation changes, on the regulation of mRNA expression. Third, we have evaluated clinical significance of microRNA, another key component of epigenomic changes, in the gene-environment interaction and have successfully found its usefulness as a pathological biomarker.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (21 results)

All 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results)

  • [Journal Article] Effect of p22phox depletion on sympathetic regulation of blood pressure in SHRSP: evaluation in a new congenic strain.2016

    • Author(s)
      Zahid HM, Ferdaus MZ, Ohara H, Isomura M, Nabika T
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 36739-36739

    • DOI

      10.1038/srep36739

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A nonsense mutation of Stim1 identified in stroke-prone spontaneously hypertensive rats decreased the store-operated calcium entry in astrocytes.2016

    • Author(s)
      Ohara H, Nabika T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 476 Issue: 4 Pages: 406-11

    • DOI

      10.1016/j.bbrc.2016.05.134

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Different effects of arginine vasopressin on high-mobility group box 1 expression in astrocytes isolated from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats.2016

    • Author(s)
      Yamagata K, Sone N, Suguyama S, Nabika T
    • Journal Title

      Int J Exp Pathol

      Volume: 97 Issue: 2 Pages: 97-106

    • DOI

      10.1111/iep.12172

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Focal ischemic injury with complex middle cerebral artery in stroke-prone spontaneously hypertensive rats with loss-of-function in NADPH oxidases2015

    • Author(s)
      Yao H, Ferdaus MZ, Zahid HM, Ohara H, Nakahara T, Nabika T
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 9 Pages: e0138551-e0138551

    • DOI

      10.1371/journal.pone.0138551

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 1A.05: COMPARISON OF THE WHOLE GENOME SEQUENCE REVEALED GENETICALLY DISTINCT LOCI BETWEEN SHR/IZM AND SHRSP/IZM.2015

    • Author(s)
      Isomura M, Saar K, Ohara H, Hübner N, Kato N, Nabika T.
    • Journal Title

      J Hypertens.

      Volume: 33 Suppl 1 Issue: Supplement 1 Pages: e2-e2

    • DOI

      10.1097/01.hjh.0000467355.97086.6a

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Investigation of Functional Genes at Homologous Loci Identified Based on Genome-wide Association Studies of Blood Lipids via High-fat Diet Intervention in Rats using an in vivo Approach.2015

    • Author(s)
      Akiyama K, Liang YQ, Isono M, Kato N
    • Journal Title

      J Atheroscler Thromb

      Volume: 22 Pages: 455-480

    • NAID

      130004704378

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of Stim1 as a candidate gene for exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat.2014

    • Author(s)
      Mohammed Zubaerul Ferdaus, Bing Xiao, Hiroki Ohara, Kiyomitsu Nemoto, Yuji Harada, Kathrin Saar, Norbert Hubner, Minoru Isomura, Toru Nabika
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 4 Pages: e95091-e95091

    • DOI

      10.1371/journal.pone.0095091

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Epigenetic changes in the brain with high-salt intervention in SHR.2016

    • Author(s)
      Shimizu-Furusawa H, Takeuchi F, Isono M, Akiyama K, Liang Y-Q, Kato N
    • Organizer
      Cardiovascular Genetics, Satellite Symposium of ISH 2016
    • Place of Presentation
      東京
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Epigenetic changes in the liver with high-fat-diet intervention in SHR.2016

    • Author(s)
      Shimizu-Furusawa H, Takeuchi F, Isono M, Akiyama K, Liang Y-Q, Kato N
    • Organizer
      Cardiovascular Genetics, Satellite Symposium of ISH 2016
    • Place of Presentation
      東京
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Epigenetic changes in the liver with dexamethasone administration in SHR.2016

    • Author(s)
      Shimizu-Furusawa H, Takeuchi F, Isono M, Akiyama K, Liang Y-Q, Kato N
    • Organizer
      Cardiovascular Genetics, Satellite Symposium of ISH 2016
    • Place of Presentation
      東京
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparison of epigenetic changes in the liver between Tg-CETP rat and SHR.2016

    • Author(s)
      Shimizu-Furusawa H, Takeuchi F, Isono M, Akiyama K, Liang Y-Q, Kato N
    • Organizer
      Cardiovascular Genetics, Satellite Symposium of ISH 2016
    • Place of Presentation
      東京
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparison of epigenetic changes in the liver between RNO4-derived congenic rat and progenitor strains.2016

    • Author(s)
      Shimizu-Furusawa H, Takeuchi F, Isono M, Akiyama K, Liang Y-Q, Kato N
    • Organizer
      Cardiovascular Genetics, Satellite Symposium of ISH 2016
    • Place of Presentation
      東京
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA methylation and hypertension.2016

    • Author(s)
      Kato N
    • Organizer
      Cardiovascular Genetics, Satellite Symposium of ISH 2016
    • Place of Presentation
      東京
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 6クラスの降圧剤間での、ラットにおける心肥大抑制と遺伝子発現変動の比較:続報.2015

    • Author(s)
      竹内史比古、磯野正人、梁一強、秋山康一、加藤規弘
    • Organizer
      第51回高血圧関連疾患モデル学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 3種のレニン–アンジオテンシン系関連降圧剤間での、ラットにおける降圧効果と腎臓での遺伝子発現変動の比較.2015

    • Author(s)
      竹内史比古、磯野正人、梁一強、秋山康一、加藤規弘
    • Organizer
      第51回高血圧関連疾患モデル学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] ラット染色体1番上の、心血管合併症遺伝子座の同定とその病態機序の探究.2015

    • Author(s)
      梁一強、秋山康一、磯野正人、竹内史比古、加藤規弘
    • Organizer
      第51回高血圧関連疾患モデル学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒトcholesteryl ester transfer proteinのトランスジェニックラットにおける肝臓での脂質代謝解析.2015

    • Author(s)
      梁一強、磯野正人、秋山康一、岡村匡史、竹内史比古、加藤規弘
    • Organizer
      第51回高血圧関連疾患モデル学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 降圧、心肥大抑制と遺伝子発現変動に関する、6クラスの降圧剤間での比較2014

    • Author(s)
      磯野正人、梁一強、秋山康一、竹内. 史比古、加藤規弘
    • Organizer
      第50回高血圧関連疾患モデル学会総会
    • Place of Presentation
      和歌山
    • Year and Date
      2014-12-05 – 2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] コンジェニック系統解析による新たな臓器障害QTLの同定2014

    • Author(s)
      加藤規弘
    • Organizer
      第50回高血圧関連疾患モデル学会総会
    • Place of Presentation
      和歌山
    • Year and Date
      2014-12-05 – 2014-12-06
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ラット染色体1番における、心血管合併症遺伝子座の多面的探索2014

    • Author(s)
      梁一強、Nitish Mehta、秋山康一、磯野正人、加藤規弘
    • Organizer
      第37回日本高血圧学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-10-17 – 2014-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Can rat genetics help to improve human genetics?2014

    • Author(s)
      Kato N
    • Organizer
      Cardiovascular Genetics Satellite 2014
    • Place of Presentation
      Rome
    • Year and Date
      2014-06-18
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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