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Clarification of the molecular mechanisms of pathogenesis caused by PBC susceptibility polymorphisms

Research Project

Project/Area Number 15K19314
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

Hitomi Yuki  東京大学, 大学院医学系研究科(医学部), 助教 (10525819)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsゲノムワイド関連解析 / 原発性胆汁性胆管炎 / 遺伝子多型 / ゲノムワイド関連解析(GWAS) / 原発性胆汁性胆管炎(PBC) / 原発性胆汁性肝硬変
Outline of Final Research Achievements

Primary biliary cholangitis (PBC) is a chronic and cholestatic liver disease that is caused by the autoimmune destruction of bile ducts.
In this study, we identified eight susceptibility gene loci for PBC by genome-wide association study (GWAS). Additionally, disease causal variants in these loci and their molecular mechanisms for disease susceptibility in PBC were clarified using Single Nucleotide Polymorphism (SNP) imputation analysis, in silico analysis, and in vitro functional analysis.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Int'l Joint Research: 9 results) Remarks (1 results)

  • [Journal Article] Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population2017

    • Author(s)
      Yasunami Michio、Nakamura Hitomi、Tokunaga Katsushi、Kawashima Minae、Nishida Nao、Hitomi Yuki、Nakamura Minoru
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 11093-11093

    • DOI

      10.1038/s41598-017-11148-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population2017

    • Author(s)
      Kawashima M, Honda M, Nakamura M. et al.
    • Journal Title

      Hum Mol Genet.

      Volume: 26 Issue: 3 Pages: 650

    • DOI

      10.1093/hmg/ddw406

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy.2016

    • Author(s)
      Sun Y, Irwanto A, Toyo-Oka L, Hong M, Liu H, Andiappan AK, Choi H, Hitomi Y, Yu G, Yu Y, Bao F, Wang C, Fu X, Yue Z, Wang H, Zhang H, Kawashima M, Kojima K, Nagasaki M, Nakamura M, Yang SK, Ye BD, Denise Y, Rotzschke O, Song K, Tokunaga K, Zhang F, Liu J.
    • Journal Title

      Sci Rep.

      Volume: 10(6) Issue: 1 Pages: 31429-31429

    • DOI

      10.1038/srep31429

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human primary biliary cirrhosis-susceptible allele of rs4979462 enhances TNFSF15 expression by binding NF-1.2015

    • Author(s)
      Hitomi Y, Kawashima M, Aiba Y, Nishida N, Matsuhashi M, Okazaki H, Nakamura M, Tokunaga K
    • Journal Title

      Human Genetics

      Volume: 印刷中 Issue: 7 Pages: 737-747

    • DOI

      10.1007/s00439-015-1556-3

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Disease susceptibility genes shared by primary biliary cirrhosis and Crohn’s disease in the Japanese population2015

    • Author(s)
      Yoshihiro Aiba, Keiko Yamazaki, Nao Nishida, Minae Kawashima, Yuki Hitomi, Hitomi Nakamura, Atsumasa Komori, Yuta Fuyuno, Atsushi Takahashi, Takaaki Kawaguchi, Masakazu Takazoe, Yasuo Suzuki, Satoshi Motoya Toshiyuki Matsui Motohiro Esaki, Takayuki Matsumoto, Michiaki Kubo, Katsushi Tokunaga, Minoru Nakamura
    • Journal Title

      Journal of Human Genetics

      Volume: 印刷中 Issue: 9 Pages: 525-531

    • DOI

      10.1038/jhg.2015.59

    • NAID

      40020589506

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Identification of the primary functional variants in primary biliary cholangitis susceptibility gene loci NFKB1/MANBA.2017

    • Author(s)
      Hitomi Y, Nakatani K, Kojima K, Nishida N, Kawai Y, Kawashima M, Aiba Y, Nagasaki M, Nakamura M, Tokunaga K.
    • Organizer
      American Society of Human Genetics
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NELFCD and CTSZ loci are associated with jaundice-stage progression in primary biliary cholangitis in the Japanese population.2017

    • Author(s)
      Kawashima M, Nishida N, Hitomi Y, Kojima K, Kawai Y, Aiba Y, Nakamura H, Nagasaki M, Tokunaga K, Nakamura M.
    • Organizer
      American Society of Human Genetics
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GWAS polygenic model approach applied to primary biliary cholangitis (PBC) in a Japanese population.2017

    • Author(s)
      Gervais O, Ueno K, Kojima K, Aiba Y, Kawashima M, Kawai Y, Hitomi Y, Tokunaga K, Nakamura M, Nagasaki M.
    • Organizer
      American Society of Human Genetics
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日本人原発性胆汁性胆管炎(PBC)感受性遺伝子領域Chr.17q12-21における機能的遺伝子多型(causal variant)の同定2017

    • Author(s)
      人見祐基、西田奈央、相葉佳洋、安波道郎、中村稔
    • Organizer
      日本肝臓学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification of the primary functional variants in primary biliary cholangitis susceptibility gene loci NFKB1/MANBA.2017

    • Author(s)
      人見祐基、仲谷健、小島要、西田奈央、河合洋介、川嶋実苗、相葉佳洋、長崎正朗、中村稔、徳永勝士
    • Organizer
      日本人類遺伝学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification of the disease causal variants in human primary biliary cholangitis (PBC) susceptibility gene loci NFKB1/MANBA.2017

    • Author(s)
      人見祐基、相葉佳洋、中村稔、徳永勝士
    • Organizer
      日本免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Principal contribution of HLA-DQ alleles, DQB1*06:04 and DQB1*03:01, to disease resistance against primary biliary cholangitis in a Japanese population.2017

    • Author(s)
      安波道朗、中村仁美、徳永勝士、川嶋実苗、西田奈央、人見祐基、中村稔
    • Organizer
      日本免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification of the causal variants in human primary biliary cirrhosis (PBC) by the combination of a genome-wide association study, whole-genome sequencing, and in silico/ in vitro functional analyses.2016

    • Author(s)
      人見祐基、相葉佳洋、中村稔、徳永勝士
    • Organizer
      日本免疫学会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県那覇市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of the primary functional variants for primary biliary cirrhosis (PBC) susceptibility loci by high-density association mapping and in silico/ in vitro functional analyses.2016

    • Author(s)
      Hitomi Y, Kojima K, Kawashima M, Kawai Y, Nishida N, Aiba Y, Yasunami M, Nagasaki M, Nakamura M, Tokunaga K.
    • Organizer
      American Society of Human Genetics
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-10-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome-wide association study identifies PRKCB as a novel genetic factor for primary biliary cirrhosis in the Japanese population.2016

    • Author(s)
      Kawashima M, Hitomi Y, Nishida N, Kojima K, Kawai Y, Nakamura H, Yasunami M, Chayama K, Aiba Y, Nagasaki M, Tokunaga K, Nakamura M, PBC Consortium in Japan (PBCCSJ).
    • Organizer
      American Society of Human Genetics
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-10-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日本人原発性胆汁性肝硬変(PBC)の発症と関連する機能的遺伝子多型(causal variant)の同定2016

    • Author(s)
      人見祐基、中村稔
    • Organizer
      日本肝臓学会
    • Place of Presentation
      東京ベイ幕張ホール(千葉県千葉市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Presentation] Imputation analysis using reference panel of 1,070 Japanese individuals (1KJPN) and in silico / in vitro functional analyses identified functional variants for primary biliary cirrhosis (PBC) susceptibility.2016

    • Author(s)
      Hitomi Y, Kojima K, Kawashima M, Kawai Y, Nishida N, Aiba Y, Yasunami M, Nagasaki M, Nakamura M, Tokunaga K.
    • Organizer
      International Congress of Human Genetics
    • Place of Presentation
      京都国際会議場(京都府京都市)
    • Year and Date
      2016-04-03
    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fine-mapping analysis of TNFSF15 across leprosy, Crohn’s disease and primary biliary cirrhosis2016

    • Author(s)
      Irwanto A, Sun Y, Hitomi Y, Toyo-oka L, Choi H, Zhang F, Song K, Tokunaga K, Liu JJ, Andiappan AK, Rotzschke O.
    • Organizer
      International Congress of Human Genetics
    • Place of Presentation
      京都国際会議場(京都府京都市)
    • Year and Date
      2016-04-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fine-mapping analysis of TNFSF15 across leprosy, Crohn’s disease and primary biliary cirrhosis.2016

    • Author(s)
      Irwanto A, Sun Y, Hitomi Y, Toyo-oka L, Choi H, Zhang F, Song K, Tokunaga K, Liu JJ, Andiappan AK, Rotzschke O.
    • Organizer
      International Congress of Human Genetics
    • Place of Presentation
      京都国際会議場(京都府京都市)
    • Year and Date
      2016-04-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ゲノムワイド関連解析から同定された日本人原発性胆汁性肝硬変発症に抑制的なHLAハプロタイプの効果2015

    • Author(s)
      安波道郎、中村仁美、徳永勝士、川嶋実苗、西田奈央、人見祐基、中村稔
    • Organizer
      日本人類遺伝学会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-10-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Dissection of HLA class II in Japanese primary biliary cirrhosis: epistasis of protective HLA-DQ allele and additional contribution of HLA-DP allele.2015

    • Author(s)
      Yasunami M, Nakamura H, Tokunaga K, Kawashima M, Nishida N, Hitomi Y, Nakamura M.
    • Organizer
      American Society for Human Genetics
    • Place of Presentation
      Boltimore(USA)
    • Year and Date
      2015-10-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 原発性胆汁性肝硬変(PBC)感受性遺伝子TNFSF15に存在するrs4979462は、NF-1結合を介したTNFSF15発現量の亢進に寄与する2015

    • Author(s)
      人見祐基、相葉佳洋、中村稔
    • Organizer
      日本肝臓学会
    • Place of Presentation
      熊本ホテルキャッスル(熊本県熊本市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 日本人原発性胆汁性肝硬変の新規疾患感受性遺伝子PRKCB, ETS1の同定2015

    • Author(s)
      相葉佳洋、川嶋実苗、西田奈央、人見祐基、小森敦正、茶山一彰、安波道郎、徳永勝士、中村稔
    • Organizer
      日本肝臓学会
    • Place of Presentation
      熊本ホテルキャッスル(熊本県熊本市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Remarks] 東京大学大学院医学系研究科人類遺伝学教室

    • URL

      http://www.humgenet.m.u-tokyo.ac.jp/

    • Related Report
      2016 Research-status Report 2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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