Analysis of PRKCB in primary biliary cholangitis based on integration analysis data
Project/Area Number |
20K08370
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Department of Clinical Research, National Hospital Organization Nagasaki Medical Center |
Principal Investigator |
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), 臨床研究センター, 研究員 (70450955)
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Co-Investigator(Kenkyū-buntansha) |
伊東 正博 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), 臨床検査科, 病理医 (30184691)
中村 稔 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), 臨床研究センター, 客員研究員 (40217906)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 原発性胆汁性胆管炎 / ゲノムワイド関連解析 / トランスクリプトーム解析 / PRKCB / 疾患感受性遺伝子 / GWAS |
Outline of Research at the Start |
申請者らは、ゲノムワイド関連解析により日本人原発性胆汁性胆管炎(PBC)の疾患感受性遺伝子の一つとしてPRKCBを同定した。しかしながら、PBCの病態形成におけるPRKCBの役割は未だ明らかではない。本研究では、ゲノムワイド関連解析と肝組織マイクロアレイの統合解析により得られたデータを基にして、PBCの病態形成におけるPRKCBの役割をin vitroとin vivoで解析する。
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Outline of Final Research Achievements |
We performed integrated analysis of various data to investigate the role of PRKCB in the pathogenesis of primary biliary cholangitis (PBC). Risk alleles of PRKCB gene polymorphisms increased the expression of PRKCB gene in B cells, monocytes, and macrophages. PRKCB protein was upregulated in B cells and monocytes/macrophages that accumulated in the portal area of PBC liver. PRKCB was inovolved in the migration of monocytes/macrophages via chemokines that were increased in the PBC liver. The expression of gene cluster co-expressed with PRKCB in the PBC liver was significantly correlated with the clinical stage, liver function, and autoantibody production. Collectively, PRKCB may be involved in the pathogenesis of PBC via B cells and monocytes/macrophages.
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Academic Significance and Societal Importance of the Research Achievements |
GWASによって約70箇所のPBC疾患感受性遺伝子領域が同定され、多くの免疫に関連する遺伝子多型がPBCの発症に関与することが明らかとなった。しかしながら、PRKCBを含めた多くのPBC疾患感受性遺伝子のPBCにおける意義や役割に関する研究はこれまで行われていない。今回の研究で、PRKCBがB細胞や単球・マクロファージを介してPBC病態形成に重要な役割をしている可能性が示唆された。PRKCBは、PBCだけではなくSLEモデルマウスの病態形成に対する関与が示唆されていることから、PBCにおけるPRKCBの解析結果は、PBCとSLEの病態形成のメカニズムを解明する上で重要な知見になると考える。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Association of soluble T cell immunoglobulin domain and mucin-3 (sTIM-3) and mac-2 binding protein glycosylation isomer (M2BPGi) in patients with autoimmune hepatitis2020
Author(s)
Kiyoshi Migita ,Minoru Nakamura,Yoshihiro Aiba,Hideko Kozuru,Seigo Abiru,Atsumasa Komori,Yuya Fujita,Junpei Temmoku,Tomoyuki Asano,Shuzo Sato,Makiko Furuya,Atsushi Naganuma,Kaname Yoshizawa,Masaaki Shimada,Keisuke Ario,Tomohiko Mannami,Hiroshi Kohno,Toshihiko Kaneyoshi,Takuya Komura,Hiromasa Ohira,Hiroshi Yatsuhashi
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Journal Title
PLoS One
Volume: -
Issue: 12
Pages: e0238540-e0238540
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 原発性胆汁性胆管炎の肝組織におけるPOU2AF1とその関連遺伝子の解析2022
Author(s)
相葉佳洋, 伊東正博, 植野和子, 人見祐基, 小森敦正, 阿比留正剛, 長岡進矢, 八橋 弘, 長崎正朗, 徳永勝士, 中村 稔
Organizer
第50回日本臨床免疫学会総会
Related Report
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[Presentation] 様々な免疫形質と関連するCD28領域におけるスプライシング制御バリアントの同定 Identification of splicing regulatory variants in multiple immunological traits-susceptibility locus CD28"2022
Author(s)
人見祐基, 相葉 佳洋, 植野 和子, 西田 奈央, 河合 洋介, 川嶋 実苗, 築地 信, 岩渕 千里, 高田 紗奈美, 三宅 紀子, 長崎 正朗, 徳永 勝士, 中村 稔
Organizer
日本人類遺伝学会第67回大会
Related Report
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[Presentation] Transcriptome and GWAS identified IL4, IL5, and GATA2 as critical upstream regulators in blood and IFNG in liver for eosinophilia in primary biliary cholangitis2022
Author(s)
植野和子, 人見祐基, 相葉佳洋, Gervais Olivier, 河合洋介, Khor Seik Soon, 川嶋実苗, 西田奈央, 小島要, 長崎正朗, 徳永勝士, 中村稔
Organizer
2022 American Society of Human Genetics
Related Report
Int'l Joint Research
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[Presentation] COLCA1 and COLCA2, the effector genes driven by rs1944919 in primary biliary cholangitis (PBC) susceptibility locus chromosome 11q23.1 in the Japanese population2021
Author(s)
Yuki Hitomi, Yoshihiro Aiba, Yosuke Kawai, Kaname Kojima, Kazuko Ueno, Nao Nishida, Minae Kawashima, Olivier Gervais, Seik-Soon Khor, Masao Nagasaki, Katsushi Tokunaga, Makoto Tsuiji, Minoru Nakamura
Organizer
APASL STC 2021
Related Report
Int'l Joint Research
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[Presentation] rs1944919 on human chromosome 11q23.1 and its effector genes COLCA1 and COLCA2 confer susceptibility to primary biliary cholangitis2021
Author(s)
Yuki Hitomi, Yoshihiro Aiba, Yosuke Kawai, Kaname Kojima, Kazuko Ueno, Nao Nishida, Minae Kawashima, Olivier Gervais, Seik-Soon Khor, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, Makoto Tsuiji
Organizer
2021 American Society for Histocompatibility and Immunogenetics Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Identification of seven primary functional variants in primary biliary cholangitis susceptibility loci in the Japanese population2021
Author(s)
Yuki Hitomi, Yoshihiro Aiba, Yosuke Kawai, Kaname Kojima, Kazuko Ueno, Nao Nishida, Minae Kawashima, Olivier Gervais, Seik-Soon Khor, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, Makoto Tsuiji
Organizer
ASHI2021
Related Report
Int'l Joint Research
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[Presentation] Applying the regional heritability mapping method to primary biliary cholangitis in the Japanese population2021
Author(s)
Olivier Gervais, Yoshihiro Aiba, Kazuko Ueno, Yosuke Kawai, Nao Nishida, Minae Kawashima, Olivier Gervais, Masao Nagasaki, Katsushi Tokunaga, Makoto Tsuiji, Minoru Nakamura
Organizer
ASHG2021
Related Report
Int'l Joint Research
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[Presentation] The analysis of POU2AF1 and its related molecules in the pathogenesis of primary biliary cholangitis by using GWAS and transcriptome datasets2020
Author(s)
Yoshihiro Aiba, Kazuko Ueno, Yuki Hitomi, Olivier Gervais, Yosuke Kawai, Minae Kawashima, Nao Nishida, Kaname Kojima, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura
Organizer
第70回アメリカ人類遺伝学会
Related Report
Int'l Joint Research
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[Presentation] Integrated GWAS and mRNA microarray analysis identified IFNG and CD40L as the central upstream regulators in primary biliary cholangitis2020
Author(s)
Kazuko Ueno, Yoshihiro Aiba, Yuki Hitomi, Shinji Shimoda, Hitomi Nakamura, Olivier Gervai, Yosuke Kawai, Seik-Soon Khor, Minae Nao Nishida, Kaname Kojima, Kawashima, Nao Nishida,Atsumasa Komori, Hiroshi Yatsuhashi, Atsushi Tanaka, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, and PBC-GWAS consortium in Japan
Organizer
ヨーロッパ肝臓学会総会
Related Report
Int'l Joint Research
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[Presentation] 原発性胆汁性胆管炎(PBC)感受性遺伝子領域Chromosome 11q23.1におけるeffector遺伝子COLCA1およびCOLCA2の同定 COLCA1/COLCA2, the effector genes in primary biliary cholangitis susceptibility locus chromosome 11q23.12020
Author(s)
人見祐基, 相葉佳洋, 河合洋介, 児島要, 植野和子, 西田奈央, 川嶋実苗, Olivier Gervais, Seik-Soon Khor,長﨑正朗, 徳永勝士, 中村稔, 築地信
Organizer
第65回日本人類遺伝学会
Related Report