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An exploratory study on the key molecules in Japanese autoimmune rheumatic diseases using genome and transcriptome analyses.

Research Project

Project/Area Number 25670458
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Collagenous pathology/Allergology
Research InstitutionUniversity of Tsukuba

Principal Investigator

TSUCHIYA Naoyuki  筑波大学, 医学医療系, 教授 (60231437)

Co-Investigator(Renkei-kenkyūsha) FURUKAWA Hiroshi  国立病院機構相模原病院, 臨床研究センター, 室長 (00372293)
OHASHI Jun  東京大学, 理学系研究科, 准教授 (80301141)
Research Collaborator KAWASAKI Aya  筑波大学, 医学医療系, 助教 (30532816)
HACHIYA Yuki  筑波大学, 大学院人間総合科学研究科
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords全身性エリテマトーデス / ANCA関連血管炎 / トランスクリプトーム / 遺伝子発現 / インターフェロン / 遺伝子発現プロファイル / ゲノム多型
Outline of Final Research Achievements

Transcriptome analyses reveal not only the key molecules in the pathogenesis, but also novel susceptibility genes which influence expression levels. Here we compared transcriptomes of Japanese patients with active systemic lupus erythematosus (SLE), ANCA-associated vasculitis (AAV) and healthy controls (HC). These groups were found to form distinct clusters. Significant enrichment of type I interferon related genes was detected not only in the differentially expressed genes in SLE, but also in AAV. Some of these genes exhibited opposite directions of expression change in SLE and AAV, suggesting that they might be related to the difference in the pathogenesis of these diseases. Furthermore, significant down-regulation of HLA class II genes was detected in AAV, suggesting that the molecular mechanism of association between HLA class II and AAV might involve reduced expression level. Thus, this exploratory study generated many testable hypotheses which should be validated in the future.

Report

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

    (9 results)

All 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (3 results) Remarks (4 results)

  • [Journal Article] Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene2014

    • Author(s)
      Gazal S, Sacre K, Allanore Y, Teruel M, Goodall AH (The CARDIOGENICS consortium), Tohma S, Alfredsson L, Okada Y, Xie G, Constantin A, Balsa A, Kawasaki A, NIicaise P, Amos C, Rodriguez-Rodriguez L, Chioccia G, Boileau C, Zhang J, Vittecoq O, Barnetche T, Gonzalez-Gay MA, Furukawa H, Cantagrel A, Le Loet X, Sumida T, Hurtado-Nedelec M, Richez C, Chollet-Martin S, Schaeverbeke T, Combe B, Khoriaty L, Coustet B, El-Benna J, Siminovitch K, Plenge R, Padyukov L, Martin J, Tsuchiya N, Dieude P
    • Journal Title

      Ann Rheum Dis

      Volume: (Published Online First) Issue: 3 Pages: e19-e19

    • DOI

      10.1136/annrheumdis-2013-204581

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of IRF5 polymorphism with MPO-ANCA positive vasculitis in a Japanese population2013

    • Author(s)
      Kawasaki A, Inoue N, Ajimi C, Sada K, Kobayashi S, Yamada H, Furukawa H, Sumida T, Tohma S, Miyasaka N, Matsuo S, Ozaki S, Hashimoto H, Makino H, Harigai M, Tsuchiya N
    • Journal Title

      Genes Immun

      Volume: 14 Issue: 8 Pages: 527-529

    • DOI

      10.1038/gene.2013.45

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] IRF2多型の全身性エリテマトーデス疾患感受性への寄与2014

    • Author(s)
      川崎綾、古川宏、近藤裕也、伊藤聡、松本功、草生真規雄、天野浩文、須田昭子、長岡章平、瀬戸口京吾、永井立夫、廣畑俊成、島田浩太、杉井章二、岡本享、千葉実行、末松栄一、岡本明子、河野肇、髙崎芳成、橋本博史、住田孝之、當間重人、土屋尚之.
    • Organizer
      第58回日本リウマチ学会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] Association of functional polymorphisms in IRF2 with systemic lupus erythematosus (SLE) In a Japanese Population.2013

    • Author(s)
      Kawasaki A, Furukawa H, Nishida N, Warabi E, Kondo Y, Ito S, Matsumoto I, Kusaoi M, Suda A, Nagaoka S, Setoguchi K, Nagai T, Hirohata S, Tokunaga K, Takasaki Y, Hashimoto H, Sumida T, Tohma S, Tsuchiya N.
    • Organizer
      2013 American College of Rheumatology Annual Scientific Meeting
    • Place of Presentation
      San Diego Convention Center(アメリカ合衆国)
    • Related Report
      2013 Research-status Report
  • [Presentation] IRF2 機能的多型と全身性エリテマトーデスの関連2013

    • Author(s)
      川崎綾、古川宏、西田奈央、蕨栄治、近藤裕也、伊藤聡、松本功、草生真規雄、須田昭子、長岡章平、瀬戸口京吾、永井立夫、廣畑俊成、徳永勝士、高崎芳成、橋本博史、住田孝之、當間重人、土屋尚之
    • Organizer
      第58回日本人類遺伝学会
    • Place of Presentation
      江陽グランドホテル(宮城県仙台市)
    • Related Report
      2013 Research-status Report
  • [Remarks] 筑波大学医学医療系 分子遺伝疫学研究室

    • URL

      http://www.md.tsukuba.ac.jp/community-med/publicmd/GE/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 筑波大学医学医療系 分子遺伝疫学研究室

    • URL

      http://www.md.tsukuba.ac.jp/community-med/publicmd/GE/

    • Related Report
      2013 Research-status Report
  • [Remarks] 自己免疫疾患のゲノム解析

    • URL

      http://www.md.tsukuba.ac.jp/community-med/publicmd/GE/research/category01/

    • Related Report
      2013 Research-status Report
  • [Remarks] メンバー 土屋尚之

    • URL

      http://www.md.tsukuba.ac.jp/community-med/publicmd/GE/member/tsuchiya.php

    • Related Report
      2013 Research-status Report

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

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