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2011 Fiscal Year Final Research Report

Clarification of genetic architecture of type 2 diabetes using expression analysis

Research Project

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Project/Area Number 21591124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokyo

Principal Investigator

HARA Kazuo  東京大学, 医学部附属病院, 特任准教授 (50359600)

Project Period (FY) 2009 – 2011
Keywords脂肪細胞 / インスリン抵抗性 / 遺伝子多型 / メタボリックシンドローム
Research Abstract

We aim to clarify genetic architecture by expression analyses using human tissues which are involved in pathogenesis of type 2 diabetes and metabolic syndrome. Paired tissue samples of visceral and subcutaneous adipose tissues were obtained from patients undergone gastric surgery. Expression analysis revealed leptin gene expression level was positively correlated with BMI and adiponectin gene expression level was negatively associated with BMI after adjustment for body mass index(BMI). Principal component analysis showed gene expression profile of visceral fat was clearly distinguished from that of subcutaneous fat, which allowed us to predict origin of sample from gene expression data set. We observed expression levels of multiple genes in visceral fat tissue were substantially increased by 5 fold and significantly increased(P<10^<-6>) compared to those in subcutaneous fat, which were enriched in genes involved in inflammatory responses. These results suggest that accumulation of visceral fat play an important role in development of metabolic syndrome and type 2 diabetes in terms of alteration in transcriptome level.

  • Research Products

    (6 results)

All 2012 2011

All Journal Article (4 results) Presentation (2 results)

  • [Journal Article] Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes2012

    • Author(s)
      Kodama K, Horikoshi M, Toda K, Yamada S, Hara K, Irie J, Sirota M, Morgan AA, Chen R, Ohtsu H, Maeda S, Kadowaki T, Butte AJ
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109(18) Pages: 7049-54

  • [Journal Article] Diabetes Genetics Replication and Meta-analysis(DIAGRAM) Consortium, Nakamura Y, Kadowaki T. A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations2012

    • Author(s)
      Imamura M, Maeda S, Yamauchi T, Hara K, Yasuda K, Morizono T, Takahashi A, Horikoshi M, Nakamura M, Fujita H, Tsunoda T, Kubo M, Watada H, Maegawa H, Okada-Iwabu M, Iwabu M, Shojima N, Ohshige T, Omori S, Iwata M, Hirose H, KakuK, Ito C, Tanaka Y, Tobe K, Kashiwagi A, Kawamori R, Kasuga M, Kamatani N
    • Journal Title

      Hum Mol Genet

      Pages: 22456796

  • [Journal Article] Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians2011

    • Author(s)
      Cho YS, Chen CH, Hu C, Long J, Ong RT, Sim X, Takeuchi F, Wu Y, Go MJ, Yamauchi T, Chang YC, Kwak SH, Ma RC, Yamamoto K, Adair LS, Aung T, Cai Q, Chang LC, Chen YT, Gao Y, Hu FB, KimHL, Kim S, Kim YJ, Lee JJ, Lee NR, Li Y, Liu JJ, Lu W, Nakamura J, Nakashima E, NgDP, Tay WT, Tsai FJ, Wong TY, Yokota M, Zheng W, Zhang R, Wang C, So WY, Ohnaka K, Ikegami H, Hara K, Cho YM, Cho NH, Chang TJ, Bao Y, Hedman AK, Morris AP, McCarthy MI ; DIAGRAM Consortium ; MuTHER Consortium, Takayanagi R, Park KS, Jia W, Chuang LM, Chan JC, Maeda S, Kadowaki T, Lee JY, Wu JY, Teo YY, Tai ES, Shu XO, Mohlke KL, Kato N, Han BG, Seielstad M
    • Journal Title

      Nat Genet

      Volume: 44(1) Pages: 67-72

  • [Journal Article] Evaluating Japanese patients with the Marfan syndrome using high-throughput microarray-based mutational analysis of fibrillin-1 gene2011

    • Author(s)
      Ogawa N, Imai Y, Takahashi Y, Nawata K, Hara K, Nishimura H, Kato M, Takeda N, Kohro T, Morita H, Taketani T, Morota T, Yamazaki T, Goto J, Tsuji S, Takamoto S, Nagai R, Hirata Y
    • Journal Title

      Am J Cardiol

      Volume: 108(12) Pages: 1801-7

  • [Presentation] Genetics of Type 2 diabetes in East Asia2011

    • Author(s)
      Hara K.
    • Organizer
      16th Japan-Korea Symposium on Diabetes Mellitus
    • Place of Presentation
      Tokyo
    • Year and Date
      2011-10-22
  • [Presentation] Comprehensive evaluation of type 2 diabetes susceptibility in the Japanese population by genome-wide imputation analysis using the 1000 Genomes Project data2011

    • Author(s)
      Hara K, Fujita H, Johnson TA, Horikoshi M, Maeda S, Tsunoda T, Kubo M, Nakamura Y, Kadowaki T.
    • Organizer
      12th ICHG/61thASHG
    • Place of Presentation
      montreal, Canada
    • Year and Date
      2011-10-12

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Published: 2013-07-31   Modified: 2015-12-10  

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