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2013 Fiscal Year Final Research Report

Genome-wide associationstudy to detect disease-associated genes in Japanese patients with primary biliary cirrhosis

Research Project

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Project/Area Number 23591006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionDepartment of Clinical Research, National Hospital Organization Nagasaki Medical Center

Principal Investigator

NAKAMURA Minoru  独立行政法人国立病院機構(長崎医療センター臨床研究センター), その他部局等, 研究員 (40217906)

Co-Investigator(Renkei-kenkyūsha) ISHIBASHI Hiromi  独立行政法人国立病院機構長崎医療センター臨床研究センター, 客員研究員 (80127969)
MIGITA Kiyoshi  独立行政法人国立病院機構長崎医療センター臨床研究センター, 部長 (60264214)
KOMORI Atsumasa  独立行政法人国立病院機構長崎医療センター臨床研究センター, 部長 (50234901)
AIBA Yoshihiro  独立行政法人国立病院機構長崎医療センター臨床研究センター, 流動研究員 (70450955)
Project Period (FY) 2011 – 2013
Keywords原発性胆汁性肝硬変 / 疾患感受性遺伝子 / GWAS / 肝臓学
Research Abstract

To identify susceptibility loci for primary biliary cirrhosis(PBC) in Japanese population, a genome-wide association study (GWAS) and subsequent replication study were performed in a total of 1327 PBC cases and 1120 healthy controls. Two significant non-HLA susceptibility loci (TNFSF15 and POU2AF1) for PBC were identified. In addition, 10 loci (CD80, IKZF3, IL7R, NFKB1, STAT4, CXCR5, TNFAIP2, MAP3K7IP1, rs6974491, DENND1B) out of 21 non-HLA susceptibility loci for PBC in European descent showed significant associations in Japanese population. These results indicated the importance of two disease-pathways in both European descent and Japanese population, Th1/Th17 differentiation of T cells (CD80, IL12A, IL12RB2, STAT4, TNFSF15) and B cells(IL7R, CXCR5, POU2AF1, SPIB, IKZF3). In addition, the study for systemic and local expression of TNF-like ligand 1A (TL1A), which is encoded by TNFSF15, indicated that TL1A may be involved in the pathogenesis of PBC.

  • Research Products

    (32 results)

All 2014 2013 2012 2011 2010

All Journal Article (16 results) Presentation (11 results) Book (5 results)

  • [Journal Article] STAT4 gene polymorphisms are associated with susceptibility and ANA status in primary biliary cirrhosis2014

    • Author(s)
      Joshita S, Umemura T, Nakamura M, Katsuyama Y, Shibata S, Kimura T, Morita S, Komatsu M, Matsumoto A, Yoshizawa K, Ishibashi H, Tanaka E, Ota M
    • Journal Title

      Dis Markers. 2014

      Volume: (Epub 2014 Feb 4.) Pages: 727393

  • [Journal Article] Chronologic changes of explanted liver volume and the use of ursodeoxycholic acid in patients with end-stage primary biliary cirrhosis2013

    • Author(s)
      Tanaka T, Yamashiki N, Sugawara Y, Tamura S, Nakamura M, Kaneko J, Aoki T, Sakamoto Y, Hasegawa K, Kokudo N
    • Journal Title

      Hepatol Res

      Volume: (Epub ahead of print)

  • [Journal Article] Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population2013

    • Author(s)
      Migita K, Nakamura M, Abiru S, Jiuchi Y, Nagaoka S, Komori A, Hashimoto S, Bekki S, Yamasaki K, Komatsu T, Shimada M, Kouno H, Hijioka T, Kohjima M, Nakamuta M, Kato M, Yoshizawa K, Ohta H, Nakamura Y, Takezaki E, Nishimura H, Sato T, Ario K, Hirashima N, Oohara Y, Naganuma A, Muro T, Sakai H, Mita E, Sugi K, Yamashita H, Makita F, Yatsuhashi H, Ishibashi H, Yasunami M
    • Journal Title

      PLoS One

      Volume: 8(8) Pages: 71382

  • [Journal Article] Systemic and local expression of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis2013

    • Author(s)
      Aiba Y, Harada K, Komori A, Ito M, Shimoda S, Nakamura H, Nagaoka S, Abiru S, Migita K, Ishibashi H, Nakanuma Y, Nishida N, Kawashima M, Tokunaga K, Yatsuhashi H, Nakamura M
    • Journal Title

      Liver Int

      Volume: (Epub ahead of print)

    • DOI

      10.1111/liv.12296

  • [Journal Article] Clinicopathological significance of serum fractalkine in primary biliary cirrhosis2013

    • Author(s)
      Harada K, Kakuda Y, Nakamura M, Shimoda S, Nakanuma Y
    • Journal Title

      Dig Dis Sci

      Volume: (Epub ahead of print)

  • [Journal Article] PBC Study Group of NHOSLJ, Nakamura M. Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients2013

    • Author(s)
      Ohishi Y, Nakamuta M, Ishikawa N, Saitoh O, Nakamura H, Aiba Y, Komori K, Migita K, Yatsuhashi H, Fukushima N, Kohjima M, Yoshimoto T, Fukuizumi K, Ishibashi M, Nishino T, Shirabe K, Taketomi A, Maehara Y, Ishibashi H
    • Journal Title

      J Gastroenterol

      Volume: (Epub ahead of print)

  • [Journal Article] Association of genes involved in bile acid synthesis with the progression of primary biliary cirrhosis in Japanese patients2013

    • Author(s)
      Inamine T, Higa S, Noguchi F, Kondo S, Omagari K, Yatsuhashi H, Tsukamoto K, Nakamura M
    • Journal Title

      J Gastroenterol

      Volume: (Epub ahead of print)

  • [Journal Article] PBC治療反応性と予後予測厚生労働省研究班による多施設のPBC研究成果2013

    • Author(s)
      中村稔
    • Journal Title

      たんじゅうさん

      Volume: 12(2) Pages: 16-17

  • [Journal Article] PBCの疾患感受性遺伝子による病態の解明2013

    • Author(s)
      中村稔
    • Journal Title

      日本消化器病学会雑誌

      Volume: 110 Pages: 1602-1610

  • [Journal Article] The Role of TL1A and DR3 in autoimmune and inflammatory diseases2013

    • Author(s)
      Aiba Y and Nakamura M
    • Journal Title

      Mediators of Inflammation

      Volume: (258164)

  • [Journal Article] Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population2012

    • Author(s)
      Nakamura M, Nishida N, Kawashima M, Aiba Y, Tanaka A, Yasunami M, Nakamura H, Komori A, Nakamuta M, Zeniya M, Hashimoto E, Ohira H, Yamamoto K, Onji M, Kaneko S, Honda M, Yamagiwa S, Nakao K, Ichida T, Takikawa H, Seike M, Umemura T, Ueno Y, Sakisaka S, Kikuchi K, Ebinuma H, Yamashiki N, Tamura S, Sugawara Y, Mori A, Yagi S, Shirabe K, Taketomi A, Arai K, Monoe K, Ichikawa T, Taniai M, Miyake Y, Kumagi T, Abe M, Yoshizawa K, Joshita S, Shimoda S, Honda K, Takahashi H, Hirano K, Takeyama Y, Harada K, Migita K, Ito M, Yatsuhashi H, Fukushima N, Ota H, Komatsu T, Saoshiro T, Ishida J, Kouno H, Kouno H, Yagura M, Kobayashi M, Muro T, Masaki N, Hirata K, Watanabe Y, Nakamura Y, Shimada M, Hirashima N, Komeda T, Sugi K, Koga M, Ario K, Takesaki E, Maehara Y, Uemoto S, Kokudo N, Tsubouchi H, Mizokami M, Nakanuma Y, Tokunaga K, Ishibashi H
    • Journal Title

      Am J Hum Genet

      Volume: 91(4) Pages: 721-728

  • [Journal Article] Involvement of Commensal Bacteria may lead to Dysregulated Inflammatory and Autoimmune Responses in a Mouse Model for Chronic Nonsuppurative Destructive Cholangitis2012

    • Author(s)
      Haruta I, Kikuchi K, Nakamura M, Hirota K, Kato H, Miyakawa H, Shibata N, Miyake Y, Hashimoto E, Shiratori K, Yagi J
    • Journal Title

      J Clin Immunol

      Volume: 32(5) Pages: 1026-37

  • [Journal Article] The role of natural killer (NK) and NK T cells in the loss of tolerance in murine primary biliary cirrhosis2012

    • Author(s)
      Shimoda S, Tsuneyama K, Kikuchi K, Harada K, Nakanuma Y, Nakamura M, Ishibashi H, Hisamoto S, Niiro H, Leung PS, Ansari AA, Gershwin ME, Akashi K
    • Journal Title

      Clin Exp Immunol

      Volume: 168 Pages: 279-284

  • [Journal Article] Serum amyloid A (SAA) induces pentraxin 3(PTX3) production in rheumatoid synoviocytes2012

    • Author(s)
      Satomura K, Torigoshi T, Koga T, Maeda Y, Izumi Y, Jiuchi Y, Miyashita T, Yamasaki S, Kawakami A, Aiba Y, Nakamura M, Komori A, Sato J, Ishibashi H, Motokawa S, Migita K
    • Journal Title

      Mod Rheumatol

      Volume: (Epub ahead of print)

  • [Journal Article] the Japanese NHO-Liver -network study group. Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization-autoimmune hepatitis prospective study)2012

    • Author(s)
      Migita K, Watanabe Y, Jiuchi Y, Nakamura Y, Saito A, Yagura M, Ohta H, Shimada M, Mita E, Hijioka T, Yamashita H, Takezaki E, Muro T, Sakai H, Nakamuta M, Abiru S, Komori A, Ito M, Yatsuhashi H, Nakamura M, Ishibashi H
    • Journal Title

      Liver Int

      Volume: 32 Pages: 837-844

  • [Journal Article] PBCの疾患感受性遺伝子による病態の解明2012

    • Author(s)
      中村稔
    • Journal Title

      日本臨床免疫学会会誌

      Volume: 35(6) Pages: 503-510

  • [Presentation] 日本人原発性胆汁性肝硬変患者におけるTLIAの役割2013

    • Author(s)
      相葉佳洋, 原田憲一, 小森敦正, 伊東正博, 阿比留正剛, 長岡進矢, 石橋大海, 中沼安二, 八橋弘, 中村稔
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2013-06-06
  • [Presentation] WHO MAY HAVE TREATMENT BENEFITS WITH FIBRATES IN PRIMARY BILIARY CIRRHOSIS : A SINGLE CENTER RETROSPECTIVE OBSERVATIONAL COHORT ANALYSIS2013

    • Author(s)
      A. Komori, M. Nakamura, Y. Aiba, Y. Kugiyama-Yasunaga, S. Bekki, R. Sasaki, S. Hashimoto, M. Ootani, S.-K. Bae, A. Saeki, S. Nagaoka, S. Abiru, K. Yamasaki, H. Ishibashi, H. Yatsuhashi
    • Organizer
      48th annual meeting of the European Association for the Study of the Liver
    • Place of Presentation
      Amsterdam, The Netherlands
    • Year and Date
      2013-04-26
  • [Presentation] 原発性胆汁性肝硬変の治療におけるフィブレート製剤の効果と限界2012

    • Author(s)
      小森敦正, 中村稔, 伊東正博, 釘山有希, 戸次鎮宗, 福島真典, 橋元悟, 大谷正史, 裵成寛, 佐伯哲, 長岡進矢, 阿比留正剛, 八橋弘, 石橋大海
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2012-06-07
  • [Presentation] 原発性胆汁性肝硬変症の病態形成におけるorganic cation transporter 1の重要性2012

    • Author(s)
      中牟田誠, 国府島庸之, 大石裕樹, 中村稔, 吉本剛志, 山崎晃裕, 中村吏, 福嶋伸良, 福泉公仁隆, 石橋大海, 本多彰, 野崎雄一, 松﨑靖司, 中島淳, 遠城寺宗近
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2012-06-07
  • [Presentation] 日本人原発性胆汁性肝硬変のゲノムワイド関連解析2012

    • Author(s)
      中村稔, 西田奈央, 川嶋実苗, 田中篤, 中牟田誠, 太田肇, 竿代丈夫, 高野弘嗣, 吉澤要, 小森敦正, 梅村武司, 銭谷幹男, 恩地森一, 橋本悦子, 大平弘正, 山本和秀, 金子周一, 山際訓, 中尾一彦, 市田隆文, 滝川一, 前原喜彦, 上本伸一, 國土典宏, 坪内博仁, 溝上雅史, 徳永勝士, 中沼安二, 石橋大海
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2012-06-07
  • [Presentation] 日本人原発性胆汁性肝硬変の病態形成に関与するHLA-A,-B,-DP,-DR遺伝子多型とCTLA-4, SLC4A2, IL12A, IRF5遺伝子多型の検討2012

    • Author(s)
      相葉佳洋, 安波道郎, 小森敦正, 右田清志, 八橋弘, 中牟田誠, 福嶋伸良, 太田肇, 石田仁也, 平田啓一, 渡部幸夫, 小松達司, 矢倉道泰, 高野弘嗣, 室豊吉, 島田昌明, 米田俊貴, 山下晴弘, 竹崎英一, 古賀満明, 小林正和, 杉和洋, 正木尚彦, 古澤要, 蒔田富士雄, 高木均, 西村英夫, 石橋大海, 中村稔
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2012-06-07
  • [Presentation] 原発性胆汁性肝硬変の病態に準拠した治療方針;当科における後ろ向き解析2011

    • Author(s)
      小森敦正,中村稔,釘山有希,戸次鎮宗,福島真典,橋元悟,大谷正史,裵成寛,佐伯哲,長岡進矢,阿比留正剛,八橋弘,伊東正博,石橋大海
    • Organizer
      第98回日本消化器病学会九州支部例会,第92回日本消化器内視鏡学会九州支部例会
    • Place of Presentation
      長崎
    • Year and Date
      20111118-19
  • [Presentation] 国立病院機構肝疾患共同研究グループにおける原発性胆汁性肝硬変合併肝細胞癌2011

    • Author(s)
      小森敦正,中村稔,阿比留正剛,八橋弘,藤岡ひかる,石橋大海
    • Organizer
      第47回日本肝癌研究会
    • Place of Presentation
      静岡
    • Year and Date
      20110728-29
  • [Presentation] 日本人原発性胆汁性肝硬変における免疫関連分子の遺伝子多型の解析2011

    • Author(s)
      相葉佳洋,稲嶺達夫,城下智,小森敦正,右田清志,八橋弘,中牟田誠,福嶋伸良,竿代丈夫,林茂樹,渡部幸夫,矢倉道泰,高野弘嗣,室豊吉,太田肇,島田昌明,米田俊貴,山下晴弘,竹崎英一,古賀満明,小松達司,小林正和,杉和洋,高橋正彦,正木尚彦,吉澤要,塚元和弘,石橋大海,中村稔
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      20110602-03
  • [Presentation] 原発性胆汁性肝硬変の自己抗体,病理学的スコア,治療反応性と予後の相関解析2011

    • Author(s)
      中村稔,伊東正博,山本和秀,太平弘正,銭谷幹男,田中篤,橋本悦子,本多政夫,金子周一,上野義之,菊池健太郎,下田慎治,小森敦正,原田憲一,向坂彰太郎,滝川一,恩地森一,西原利治,大西三朗,坪内博仁,中沼安二,石橋大海
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      20110602-03
  • [Presentation] Positive Anti-GP210 Antibodies is a Risk Factor for Poor Biochemical Response to Ursodeoxycholic Acid Treatment in Japanese Patients with Primary Biliary Cirrhosis. 46th Annual Meeting of the European Association for the Study of the Liver2011

    • Author(s)
      M. Nakamura, M. Ito, K. Yamamoto, M. Zeniya, H. Ohira, E. Hashimoto, M. Honda, S. Kaneko, Y. Ueno, K. Kikuchi, S. Onji, S. Shimoda, H. Takikawa, A. Tanaka, A. Komori, H. Yatsuhashi, H. Kondo, K. Harada, S. Onishi, H. Tsubouchi, Y. Nakanuma, H. Ishibashi
    • Organizer
      The International Liver Congress 2011
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      20110330-0403
  • [Book] ゲノムワイド関連解析による日本人原発性胆汁性肝硬変の疾患感受性遺伝子、TNFSF15、POU2AF1の同定分子消化器病2013

    • Author(s)
      中村稔
    • Total Pages
      85-89
    • Publisher
      先端医学社
  • [Book] PBCの疾患感受性遺伝子による病態の解明.特集:ゲノムワイド関連解析からみえてきた消化器疾患2012

    • Author(s)
      中村稔
    • Total Pages
      27-32
    • Publisher
      G.I.Research
  • [Book] PBCの疾患感受性遺伝子による病態の解明2012

    • Author(s)
      中村稔
    • Total Pages
      213-218
    • Publisher
      C.I.Research
  • [Book] 遺伝子多型は自己免疫性肝胆道疾患の病態にせまれるか分子消化器病2011

    • Author(s)
      中村稔、石橋大海
    • Total Pages
      7-13
    • Publisher
      先端医学社 (発行者 : 鯨岡哲)
  • [Book] 核膜康複合体タンパク質Gp210生体の科学細胞核-構造と機能2010

    • Author(s)
      中村稔、相葉佳洋
    • Total Pages
      366-369
    • Publisher
      (財)金原一郎記念医学医療振興財団

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Published: 2015-07-16  

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