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1996 Fiscal Year Final Research Report Summary

Identification of NIDDM susceptibility genes in the Japanese population by candidate gene approach and whole genome mapping.

Research Project

Project/Area Number 07457220
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionUniversity of Tokyo

Principal Investigator

KADOWAKI Takashi  University of Tokyo.Assistant, 医学部・附属病院・第三内科, 助手 (30185889)

Co-Investigator(Kenkyū-buntansha) MORI Yasumichi  University of Tokyo, medical staff, 医学部・附属病院・第三内科, 医員
ETO Kazuhiro  University of Tokyo, medical staff, 医学部・附属病院・第三内科, 医員
YASUDA Kazuki  University of Tokyo, medical staff, 医学部・附属病院・第三内科, 医員
Project Period (FY) 1995 – 1996
KeywordsCommon NIDDM / sib pair analysis / whole genome mapping / candidate genes / beta3 adrenergic receptor / obesity / UCP / PPARgamma
Research Abstract

1.Common NIDDM gene mapping.
We attempt to employ affected sib pair analysis for the identification of common NIDDM genes. We have collected DNA sample from 250 affected sib pairs of NIDDM from outpatients clinic of Tokyo Unibersity Hospital. We have also gathered the detailed clinical information such as family history, obesity, age of onset, insulin secretory capacity and treatment modality for all of the affected sib pairs. We plan to initiate whole genome mapping using microsatellite markers located every 10cM on the genome. We Iso started analysis of candidate Ioci revealed in the similar studies in other ethnic groups such as NIDDM1 and NIDDM2. We found that these loci are not the major Ioci for NIDDM susceptibility in the Japanese population.
2.Candidate gene approach
We studied several candidate genes for obesity, the most important risk factor for NIDDM in Japan. We identified several mutations in the genes for in the beta3 adrenergic receptor, UCP-1,3 and PPARgamma and are in the process of carrying out functional analysis and association studies. Among these, Trp64Arg mutation in the beta3 adrenergic receptor was found to be associated with higher BMI and increased visceral adiposity.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Yanagisawa,K.: "Mutation in the mitcchcndrial tRNA^<Leu> at position 3243 and sponanas abortions in Japanese women attending a clinic for diabetic pregnanies" Diabetologia. 38. 809-815 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuda,K.: "No evidence for mutations in a putative subunit of the beta-cell ATP-sensitive potassium channel in Japanese NIDDM patients" Biochem.Biophys.Res.Commun.211. 1036-1040 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kadowaki,H.: "A mutation in the b3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese Subjects." Biochem.Biophys.Res.Commun.210. 555-560 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terauchi,Y.: "Pancreatic-Cell-Specitic targeted disruption of glucokinase gene." J.Biol.Chem.270. 30253-30256 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Aizawa,T.: "Analysis of poncreatic b cell in the mouse with targeted disneption of the pancreatic b cell-specitic glucokinase gene." Biochem.Biophys.Res.Commun.229. 460-465 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Terauchi,Y.: "Development of non-insulin-dependent diabetes mellifus in the double Knockout mice with disruption of insulin receptor substrate 1 and b-cell glucckinase genes : genetic reconstitution of diabetesas a polygenic disease" J.Clin.Invest.99. 861-866 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim-Motoyama,H.: "Serum leptin levels are associated with hyperinsulinemia independent of body mass index but not with visceral obesity." Biochem.Biophys.Res.Commun.239. 340-344 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim-Motoyama,H.: "A mutation of the b3-adrenargic receptor is associated with visceral obesity but decreased serum triglyceride." Diabetologia. 40. 469-472 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,Y.: "A homozygous kinase-detective mutation in the insulin receptor gene in a patient with leprechaunism." Diabetologia. 40. 412-420 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,Y.: "Two aberrant splicings caused by mutations in the insulin receptor gene in cultured lymphocytes from a patient with Rabson-Menden hall's syndrome." J.Clin.Invest.101. 588-594 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanagisawa, K.: "Mutation in the mitochondrial tRNA^<Leu> at position 3243 and spontaneous abortions in Japanese women attending a clinic for diabetic pregnancies." Diabetologia. 38. 809-815 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasuda, K.: "No evidence for mutations in a putative subnit of the beta-cell ATP-sensitive potassium channel in Japanese NIDDM patients." Biochem.Biophys.Res.Commun.211. 1036-1040 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kadowaki, H.: "A mutation in the b3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects." Biochem.Biophys.Res.Commun.210. 555-560 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terauchi, Y.: "Pancreatic-Cell-specific targeted disruption of glucokinase gene." J.Biol.Chem.270. 30253-30256 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Aizawa, T.: "Analysis of pancreatic b cell in the mouse with targeted disruption of the pancreatic b cell-specific glucokinase gene." Biochem.Biophys.Res.Commun.229. 460-465 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terauchi, Y.: "Development of non-insulin-dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate-1 and b-cell glucokinase genes : genetic reconstitution of diabetes as a polygenic disease." J.Clin.Invest.99. 861-866 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kim-Motoyama, H.: "Serum leptin levels are associated with hyperinsulinemia independent of body mass index but not with visceral obesity." Biochem.Biophys.Res.Commun.239. 340-344 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kim-Motoyama, H.: "A mutation of the b3-adrenergic receptor is associated with visceral obesity but decreased serum triglyceride." Diabetologia. 40. 469-472 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, Y.: "A homozygous kinase-defective mutation in the insulin receptor gene in a patient with leprechaunism." Diabetologia. 40. 412-420 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, Y.: "Two aberrant splicings caused by mutations in the insulin receptor gene in cultured lymphocytes from a patient with Rabson-Mendenhall's syndrome." J.Clin.Invest.101. 588-594 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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