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The search and prospective follow-up study of genetic predisposition and environmental factors of ectopic fat accumulation

Research Project

Project/Area Number 25461343
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionOsaka University (2015)
Kyoto University (2013-2014)

Principal Investigator

Hotta Kikuko  大阪大学, 医学部附属病院, 講師 (30360639)

Co-Investigator(Kenkyū-buntansha) KITAMOAO Takuya  京都大学, 大学院医学研究科, 特定技術職員 (10456882)
KITAMOAO Aya  京都大学, 大学院医学研究科, 教務補佐 (30381627)
Co-Investigator(Renkei-kenkyūsha) YONEDA Masato  横浜市立大学, 大学病院, 助教 (10423831)
HYOGO Hideyuki  広島大学, 学内共同利用施設等, 助教 (40397930)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords非アルコール性脂肪肝疾患 / 内臓脂肪蓄積 / 次世代シークエンサー / エピゲノム / 遺伝子多型 / メタボリックシンドローム / RNAシークエンス / メチル化DNA / メチル化 / PNPLA3 / ターゲット・リシークエンス
Outline of Final Research Achievements

Genome-wide association study (GWAS) was performed and revealed that SNP rs738409 in the PNPLA3 plays a key role in the development of non-alcoholic fatty liver disease (NAFLD). We performed targeted next-generation sequence analysis and fine mapping of the linkage disequilibrium block containing PNPLA3 rs738409 and found that polymorphisms in the encoding the SAMM50 and PARVB are associated with the development and progression of NAFLD as well. We performed targeted-bisulfite sequencing and found that hypomethylation of CpG26 and hypermethylation of CpG99 may contribute to the severity of fibrosis in NAFLD. The levels of CpG99 methylation and PNPLA3 mRNA were affected by the rs738409 genotype.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (18 results)

All 2016 2015 2014 2013

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (11 results)

  • [Journal Article] <i>CDH13</i> Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome Traits Independently of Visceral Fat Mass2016

    • Author(s)
      Kitamoto A, Kitamoto T, Nakamura T, Matsuo T, Nakata Y, Hyogo H, Ochi H, Kamohara S, Miyatake N, Kotani K, Mineo I, Wada J, Ogawa Y, Yoneda M, Nakajima A, Funahashi T, Miyazaki S, Tokunaga K, Masuzaki H, Ueno T, Chayama K, Hamaguchi K, Yamada K, Hanafusa T, Oikawa S, Sakata T, Tanaka K, Matsuzawa Y, Hotta K.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 23 Issue: 3 Pages: 309-319

    • DOI

      10.5551/jat.31567

    • NAID

      130005131888

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus.2016

    • Author(s)
      Kan H, Hyogo H, Ochi H, Hotta K, Fukuhara T, Kobayashi T, Naeshiro N, Honda Y, Kawaoka T, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Aikata H, Chayama K
    • Journal Title

      Hepatol Res

      Volume: 46 Issue: 3 Pages: 146-153

    • DOI

      10.1111/hepr.12552

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The characteristics of non-obese NAFLD: Effect of genetic and environmental factors.2016

    • Author(s)
      Honda Y, Yoneda M, Kessoku T, Ogawa Y, Tomeno W, Imajo K, Mawatari H, Fujita K, Hyogo H, Ueno T, Chayama K, Saito S, Nakajima A, Hotta K
    • Journal Title

      Hepatol Res

      Volume: - Issue: 10 Pages: 636-636

    • DOI

      10.1111/hepr.12648

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <i>ADIPOQ</i> polymorphisms are associated with insulin resistance in Japanese women2015

    • Author(s)
      KitamotoA, KitamotoT, SoR, MatsuoT, NakataY, HyogoH, OchiH, NakamuraT, KamoharaS, MiyatakeN, KotaniK, MineoI, WadaJ, OgawaY, YonedaM, NakajimaA, FunahashiT, MiyazakiS, TokunagaK, MasuzakiH, UenoT, ChayamaK, HamaguchiK, YamadaK, HanafusaT, OikawaS, SakataT, TanakaK, MatsuzawaY, HottaK.
    • Journal Title

      Endocrine Journal

      Volume: 62 Issue: 6 Pages: 513-521

    • DOI

      10.1507/endocrj.EJ14-0574

    • NAID

      130005085774

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Targeted-bisulfite sequence analysis of the methylation of CpG islands in genes encoding PNPLA3, SAMM50, and PARVB of patients with nonalcoholic fatty liver disease.2015

    • Author(s)
      Kitamoto T, Kitamoto A, Ogawa Y, Honda Y, Imajo K, Saito S, Yoneda M, Nakamura T, Nakajima A, Hotta K.
    • Journal Title

      J Hepatol

      Volume: 印刷中 Issue: 2 Pages: 494-502

    • DOI

      10.1016/j.jhep.2015.02.049

    • NAID

      120005690144

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits2014

    • Author(s)
      Kitamoto A, Kitamoto T, Nakamura T, Ogawa Y, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, Nakao K, Sekine A, Chayama K, Nakajima A, Hotta K
    • Journal Title

      Endocrine Journal

      Volume: 8

    • NAID

      130004677938

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeted next-generation sequencing and fine linkage disequilibrium mapping reveals association of PNPLA3 and PARVB with the severity of nonalcoholic fatty liver disease2014

    • Author(s)
      Kitamoto T, Kitamoto A, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, Nakao K, Sekine A, Chayama K, Nakajima A, Hotta K
    • Journal Title

      Journal of Human Genetics

      Volume: 6 Issue: 5 Pages: 241-6

    • DOI

      10.1038/jhg.2014.17

    • NAID

      120005477223

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 非アルコール性脂肪肝疾患(NAFLD)のエピゲノム解析2015

    • Author(s)
      堀田紀久子、北本卓也、北本綾、小川祐二、中島淳
    • Organizer
      日本人類遺伝学会第60回大会
    • Place of Presentation
      東京都新宿区
    • Year and Date
      2015-10-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非アルコール性脂肪肝疾患のエピゲノム解析2015

    • Author(s)
      堀田紀久子、小川祐二、本多靖、米田正人、中島淳
    • Organizer
      第36回日本肥満学会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非アルコール性脂肪肝疾患(NAFLD)のエピゲノム解析2015

    • Author(s)
      堀田紀久子、北本卓也、北本綾、小川裕二、米田正人、中島 淳
    • Organizer
      第2回肝臓と糖尿病・代謝研究会
    • Place of Presentation
      山口県下関市
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Presentation] 非アルコール性脂肪肝疾患感受性領域の次世代シークエンサーによるターゲットリシークエンス2014

    • Author(s)
      堀田紀久子,北本卓也,北本綾,兵庫秀幸,越智秀典,上野隆登,茶山一彰,米田正人,小川裕二,中島淳
    • Organizer
      日本人類遺伝学会第59回大会
    • Place of Presentation
      東京都江戸川区
    • Year and Date
      2014-11-19 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] GCKR、TRIB1の遺伝子多型とメタボリックシンドローム及び非アルコール性脂肪肝疾患との関連2014

    • Author(s)
      堀田紀久子,北本綾,北本卓也,小川裕二,米田正人, 上野隆登,兵庫秀幸,越智秀典,茶山一彰,中島淳
    • Organizer
      第35回日本肥満学会
    • Place of Presentation
      宮崎県宮崎市
    • Year and Date
      2014-10-24 – 2014-10-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Targeted next-generation sequencing and fine linkage disequilibrium mapping reveals association of PNPLA3 and PARVB with the severity of nonalcoholic fatty liver disease2014

    • Author(s)
      Hotta K, Kitamoto T, Kitamoto A, Yoneda M, Hyogo H, Ochi H, Ueno T, Chayama K, Nakajima A
    • Organizer
      th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
    • Place of Presentation
      京都府京都市
    • Year and Date
      2014-09-12 – 2014-09-14
    • Related Report
      2014 Research-status Report
  • [Presentation] 非アルコール性脂肪肝炎感受性領域の次世代シークエンサーによるターゲットリシークエンス2014

    • Author(s)
      堀田紀久子,北本綾,北本卓也,小川裕二,米田正人, 上野隆登,兵庫秀幸,越智秀典,茶山一彰,中島淳
    • Organizer
      第57回日本糖尿病学会
    • Place of Presentation
      大阪府大阪市
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] シンポジウム4:肥満症の成因と疫学~成因のコントロールによる効果的な予防~肥満症の遺伝素因2013

    • Author(s)
      堀田紀久子
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 非アルコール性脂肪肝炎のゲノムワイド関連解析2013

    • Author(s)
      堀田紀久子、中尾一和
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Related Report
      2013 Research-status Report
  • [Presentation] 特別シンポジウム4:糖尿病関連遺伝子研究の進化 肥満及び肥満症関連遺伝子2013

    • Author(s)
      堀田紀久子
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Related Report
      2013 Research-status Report
  • [Presentation] ウエスト:ヒップ比及びBMI感受性遺伝子多型の内臓脂肪および皮下脂肪面積に及ぼす効果2013

    • Author(s)
      堀田紀久子、松尾知明、中田由夫、兵庫秀幸、越智秀典、蒲原聖可、小谷一晃、伊藤直人、嶺尾郁夫、和田淳、米田正人、中島淳、船橋徹、宮崎滋、徳永勝人、益崎裕章、茶山一彰、上野隆登、浜口和之、山田研太郎、花房俊昭、及川眞一、坂田利家、田中喜代次、松澤佑次、中尾一和
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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