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2011 Fiscal Year Final Research Report

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

Research Project

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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
Keywordsゲノムワイド関連解析 / C型肝炎
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

  • Research Products

    (16 results)

All 2012 2011 Other

All Journal Article (5 results) Presentation (8 results) Book (2 results) Remarks (1 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 Pages: 1131-1138

    • DOI

      doi:10.1038/ng.970

  • [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 Pages: e24221

    • DOI

      doi:10.1371/journal.pone.0024221

  • [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 Pages: 990-995

    • DOI

      doi:10.1038/ng.939

  • [Journal Article] Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma2011

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

      Nature genetics

      Volume: 43 Pages: 455-458

    • DOI

      doi:10.1038/ng.809

  • [Journal Article] A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population2011

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

      Human molecular genetics

      Volume: 20 Pages: 3884-3892

    • DOI

      doi:10.1093/hmg/ddr301

  • [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
    • Year and Date
      20120000
  • [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
    • Year and Date
      20110000
  • [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
    • Year and Date
      20110000
  • [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
    • Year and Date
      20110000
  • [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
    • Year and Date
      20110000
  • [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
    • Year and Date
      20110000
  • [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
    • Year and Date
      20110000
  • [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
    • Year and Date
      20110000
  • [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
  • [Book] 肝疾患Review2012-2013HBV感染のGWAS解析

    • Publisher
      日本メディカルセンター
  • [Remarks]

    • URL

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

URL: 

Published: 2013-07-31  

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