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Evaluation of MICA variations and serum MICA as prognostic factors for Chronic hepatitis C patients

Research Project

Project/Area Number 23651192
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical genome science
Research InstitutionThe University of Tokyo

Principal Investigator

MATSUDA Koichi  東京大学, 医科学研究所, 准教授 (90401257)

Project Period (FY) 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywordsゲノムワイド関連解析 / C型肝炎 / MICA / 肝癌 / HCV
Research Abstract

Here we conducted a genome-wide association study using 1618 HCV-induced liver cirrhosis(LC) cases and 4, 854 CHC patients. We found that two SNPs within the major histocompatibility complex(MHC) region, rs910049 and rs3135363, and were significantly associated with the progression from CHC to LC(Pcombined=9. 15x10^<-11> and 1. 45x10^<-10>). We also screened 15 candidate SNPs at the promoter region and found that SNP rs2596538 located at 2. 8 kb upstream of the MICA gene altered the binding of transcription factor SP1 to the genomic region including this SNP. Moreover, higher transcriptional activity of G allele was observed in vitro by luciferase reporter assay, concordant with higher soluble MICA(sMICA) level among HCV-induced HCC patients with G allele. In summary, we identified the crucial roles of multiple genetic variations within the MHC region as prognostic/predictive biomarkers for CHC patients

Report

(2 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (22 results)

All 2012 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (11 results) Book (4 results) Remarks (2 results)

  • [Journal Article] Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma2011

    • Author(s)
      J. C. Chambers, W. Zhang, J. Sehmi, X. Li, M. N. Wass, P. Van der Harst, H. Holm, S. Sanna, M. Kavousi, S. E. Baumeister, L. J. Coin, G. Deng, C. Gieger, N. L. Heard-Costa, J. J. Hottenga, B. Kuhnel, V. Kumar, V. Lagou, L. Liang, J. Luan, P. M. Vidal, I. Mateo Leach, P. F. O' Reilly, J. F. Peden, N. Rahmioglu, P. Soininen, E. K. Speliotes, X. Yuan, G. Thorleifsson, B. Z. Alizadeh, L. D. Atwood, I. B. Borecki, M. J. Brown, P. Charoen, F. Cucca, D. Das, E. J. de Geus, A. L. Dixon, A. Doring, G. Ehret, G. I. Eyjolfsson, M. Farrall, N. G. Forouhi, N. Friedrich, W. Goessling, D. F. Gudbjartsson, T. B. Harris, A. L. Hartikainen, S. Heath, G. M. Hirschfield, A. Hofman, G. Homuth, E. Hypponen, H. L. Janssen, T. Johnson, A. J. Kangas, I. P. Kema, J. P. Kuhn, S. Lai, M. Lathrop, M. M. Lerch, Y. Li, T. J. Liang, J. P. Lin, R. J. Loos, N. G. Martin, M. F. Moffatt, G. W. Montgomery, P. B. Munroe, K. Musunuru, Y. Nakamura, C. J. O' Donnell, I. Olafsson, B. W. Penninx, A. Pouta, B. P. Prins, I. Prokopenko, R. Puls, A. Ruokonen, M. J. Savolainen, D. Schlessinger, J. N. Schouten, U. Seedorf, S. Sen-Chowdhry, K. A. Siminovitch, J. H. Smit, T. D. Spector, W. Tan, T. M. Teslovich, T. Tukiainen, A. G. Uitterlinden, M. M. Van der Klauw, R. S. Vasan, C. Wallace, H. Wallaschofski, H. E. Wichmann, G. Willemsen, P. Wurtz, C. Xu, L. M. Yerges-Armstrong, G. R. Abecasis, K. R. Ahmadi, D. I. Boomsma, M. Caulfield, W. O. Cookson, C. M. van Duijn, P. Froguel, K. Matsuda, M. I. McCarthy, C. Meisinger, V. Mooser, K. H. Pietilainen, G. Schumann, H. Snieder, M. J. Sternberg, R. P. Stolk, H. C. Thomas, U. Thorsteinsdottir, M. Uda, G. Waeber, N. J. Wareham, D. M. Waterworth, H. Watkins, J. B. Whitfield, J. C. Witteman, B. H. Wolffenbuttel, C. S. Fox, M. Ala-Korpela, K. Stefansson, P. Vollenweider, H. Volzke, E. E. Schadt, J. Scott, M. R. Jarvelin, P. Elliott, J. S. Kooner
    • Journal Title

      Nature genetics

      Volume: 43 Issue: 11 Pages: 1131

    • DOI

      10.1038/ng.970

    • URL

      https://pure.teikyo.jp/en/publications/7fd5cd6f-7ff6-428e-86ab-8cc11153cd3f

    • Related Report
      2011 Final Research Report
  • [Journal Article] Associations of HLA-DP variants with hepatitis B virus infection in southern and northern Han Chinese populations : a multicenter case-control study2011

    • Author(s)
      J. Li, D. Yang, Y. He, M. Wang, Z. Wen, L. Liu, J. Yao, K. Matsuda, Y. Nakamura, J. Yu, X. Jiang, S. Sun, Q. Liu, Q. Song, M. Chen, H. Yang, F. Tang, X. Hu, J. Wang, Y. Chang, X. He, Y. Chen, J. Lin
    • Journal Title

      PloS one

      Volume: 6 Issue: 8 Pages: e24221-e24221

    • DOI

      10.1371/journal.pone.0024221

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Large-scale genome-wide association studies in east Asians identify new genetic loci influencing metabolic traits2011

    • Author(s)
      Y. J. Kim, M. J. Go, C. Hu, C. B. Hong, Y. K. Kim, J. Y. Lee, J. Y. Hwang, J. H. Oh, D. J. Kim, N. H. Kim, S. Kim, E. J. Hong, J. H. Kim, H. Min, Y. Kim, R. Zhang, W. Jia, Y. Okada, A. Takahashi, M. Kubo, T. Tanaka, N. Kamatani, K. Matsuda, T. Park, B. Oh, K. Kimm, D. Kang, C. Shin, N. H. Cho, H. L. Kim, B. G. Han, Y. S. Cho
    • Journal Title

      Nature genetics

      Volume: 43 Issue: 10 Pages: 990-995

    • DOI

      10.1038/ng.939

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma2011

    • Author(s)
      Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, Otsuka M, Tateishi R, Omata M, Nakagawa H, Koike K, Kamatani N, Kubo M, Nakamura Y, Matsuda K
    • Journal Title

      Nat Genet.

      Volume: 43 Issue: 5 Pages: 455-8

    • DOI

      10.1038/ng.809

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population2011

    • Author(s)
      Mbarek H, Ochi H, Urabe Y, Kumar V, Kubo M, Hosono N, Takahashi A, Kamatani Y, Miki D, Abe H, Tsunoda T, Kamatani N, Chayama K, Nakamura Y, Matsuda K
    • Journal Title

      Hum Mol Genet

      Volume: 20 Issue: 19 Pages: 3884-3892

    • DOI

      10.1093/hmg/ddr301

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Presentation] ゲノムワイド関連解析による癌感受性遺伝子の探索2012

    • Author(s)
      松田浩一
    • Organizer
      文科省がん支援活動・厚労省対がん10カ年研究合同公開シンポジウム
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2012-01-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] ゲノムワイド関連解析による癌感受性遺伝子の探索2012

    • Author(s)
      松田浩一
    • Organizer
      文科省がん支援活動・厚労省対がん10カ年研究合同公開シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] ゲノムワイド関連解析による肝癌発症関連遺伝子MICAの同定2011

    • Author(s)
      松田浩一
    • Organizer
      日本人類遺伝学会
    • Place of Presentation
      千葉
    • Year and Date
      2011-11-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Genome wide association study identifies MICA variant as a susceptibility loc for HCV-induced hepatocellualr carcinoma2011

    • Author(s)
      松田浩一
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Impact of genetic variations on disease susceptibility and various quantitative traits2011

    • Author(s)
      Koichi Matsuda
    • Organizer
      The 18th East Asia Joint Symposium on Biomedical Research
    • Place of Presentation
      Shanghai
    • Related Report
      2011 Final Research Report
  • [Presentation] 癌における個別化医療の現状と今後の展望2011

    • Author(s)
      松田浩一
    • Organizer
      第61回日本体質学会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Genome-wide association study identifies MICA variant as a susceptibility locus for HCV-induced hepatocellular carcinoma2011

    • Author(s)
      Koichi Matsuda, Vinod Kumar, Yusuke Nakamura
    • Organizer
      第56会日本人類遺伝学会
    • Place of Presentation
      幕張
    • Related Report
      2011 Final Research Report
  • [Presentation] A genome-wide association study identified novel susceptible loci for HCV-induced Liver cirrhosis2011

    • Author(s)
      Yuji Urabe, Koichi Matsuda, Naoya Kato, Kazuaki Chayama, Yusuke Nakamura
    • Organizer
      第56会日本人類遺伝学会
    • Place of Presentation
      幕張
    • Related Report
      2011 Final Research Report
  • [Presentation] A Genome-Wide Association Study of Chronic Hepatitis B Identified Novel Risk Locus in a Japanese Population2011

    • Author(s)
      Hamdi Mbarek, Hidenori Ochi, Yuji Urabe, Yusuke Nakamura, Koichi Matsuda
    • Organizer
      第56会日本人類遺伝学会
    • Place of Presentation
      幕張
    • Related Report
      2011 Final Research Report
  • [Presentation] A genome-wide association study identified novel susceptible loci for HCV-induced Liver cirrhosis2011

    • Author(s)
      Yuji Urabe, Koichi Matsuda, Naoya Kato, Kazuaki Chayama, Yusuke Nakamura
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] Genome Wide Association Study of HCV-induced Hepatocellular carcinoma2011

    • Author(s)
      Koichi Matsuda, Vinod Kumar, Yusuke Nakamura
    • Organizer
      102th American association of cancer research
    • Place of Presentation
      Orland, USA
    • Related Report
      2011 Final Research Report
  • [Book] GWASによる癌オーダーメイド医療の実現に向けて2012

    • Author(s)
      松田浩一
    • Publisher
      先端医学社(印刷中)
    • Related Report
      2011 Annual Research Report
  • [Book] 肝疾患Review 2012-2013 HBV感染のGWAS解析2012

    • Author(s)
      松田浩一
    • Publisher
      日本メディカルセンター(印刷中)
    • Related Report
      2011 Annual Research Report
  • [Book] GWASによる癌オーダーメイド医療の実現に向けて

    • Publisher
      先端医学社
    • Related Report
      2011 Final Research Report
  • [Book] 肝疾患Review2012-2013HBV感染のGWAS解析

    • Publisher
      日本メディカルセンター
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/nakamura/matsuda/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/nakamura/matsuda/index.html

    • Related Report
      2011 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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