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骨代謝の多様性に関する分子生物学的検討

Research Project

Project/Area Number 09671028
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

細井 孝之  東京大学, 医学部・附属病院, 講師 (40240709)

Co-Investigator(Kenkyū-buntansha) 星野 真二郎  東京大学, 医学部・附属病院, 医員
明渡 陽子  東京大学, 医学部附属病院, 医員
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords骨粗鬆症 / 遺伝子塑性 / 骨代謝 / エストロゲン受容体 / 副甲状腺ホルモン / アポクポプロテイン / ビタミンD受容体 / コラーゲン / 遺伝子多型性 / 骨量 / 骨祖鬆症 / エストロゲンレセプター / 分子生物学
Research Abstract

複数の遺伝的素因と環境因子との相互作用の中で発症する骨粗鬆症の病態を解明する作業において、遺伝的素因を分子生物学的に明らかにすることの意義は大きい。本研究では、骨粗鬆症の病態形成に関与する遺伝子群を遺伝子多型性を用いてスクリーニングし、病態との関連を解析を行うことによって骨粗鬆症の病態解析にアプローチした。
骨粗鬆症は、他の生活習慣病、つまり、高血圧、動脈硬化、糖尿病などと同様に、多因子性疾患の一つといえる。これらの疾患を予防し、発症したのちに適切な治療を行うためには、その病態を詳細に把握する必要がある。本研究は原因遺伝子を広い候補遺伝子群から、それらの多型性を用いてスクリーニングし、分子生物学的に病態の根本をさぐる点に意義をもつ。
我々はエストロゲン受容体が果たす骨代謝における重要性を鑑み、エストロゲン受容体遺伝子の多型性と閉経後女性の骨量との間に世界に先駆けて検討して有意な関連を見出し、発表した。さらに骨粗鬆症の多因子性をふまえた複数の候補遺伝子の多型性を用いての解析を大規模な集団について行い、成果をあげた。

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Yamada Y、Harada A、Hosoi T、et al: "Prediction of the outcome of therapy with active Vitamin D for postmenopausal osteoporosis by TGF-betal genotype"J Bone Miner Res. (in press).

    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima T、Ota H、Shirai T et al: "Ethnic difference in contribution of Spl Site variation of COLIAI gene in genetic predisposition to osteoporosis"Calcified Tissue Int. 65. 352-353 (1999)

    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogawa S、Urano T、Hosoi T、et al: "Association of bone mineral density with a polymorphism of the peroxisome proliferator-activated receptor gammagene : PPAR gnmim"Biochem Biophys Res Commun. 260. 122-126 (1999)

    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada Y、Hosoi T、Makimoto F、et al: "Transforming growth factor betal gene polymorphism and bone mineral density in Japanese adolescents"Am J Med. 106. 477-479 (1999)

    • Related Report
      1998 Final Research Report Summary
  • [Publications] Urano T、Yashiroda H、Muraoka M et al: "p57(kip2) is degraded throng in the proteasure in osteoblasts stimulated proliferation by transforming growth factor beta 1"J Biol Chem. 274. 12197-12200 (1999)

    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosoi T、Miyao M、Inoue S et al: "Association study of parathyroid hormone gene polymorphism and bone-mineral density in Japanese postmenopausal women"Calcified Tissue International. 64. 205-208 (1999)

    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosoi,T.et al.: "Association study of parathyroid hormone gene polymorphism and bone mineral donsity in Jnpanese postmerepansul women" Calcif Tissue Int.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada,Y et al: "TGFβ1 gene polymorphism and bone mineral density in Japanese adolescents" Am J Med.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsukamoto,K et al.: "Association of bone mineral density with CA repeat polymorphism of the human interlenkin 6 gene in Japanese" Jpn J Hum Genet. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogawa,S.et al.: "Molecular cloning and charaterization of human estrosen receptor β cx : a potential inhibitor of estrogen action in human" Nucleic Acid Res. vol26,No15. 3502-3512 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyao,M et al.: "Polymorphism of insulin-like growth factor I gene and bone mineral density" Calcif Tissue Int.vol63.no4. 306-311 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsukamoto,K.et al: "Isolation and radiation hybrid mapping of dinucfeotide repeat polymorphism at the human estrogen receptor β locus" Jpn J Hum Genet. vol43. 73-74 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 細井 孝之編著: "本音で語る骨粗鬆症の診療" 永井書店, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogawa,S.et al.: "Gross inhibition of both estrogen receptor α and β,pathways by each dominant negative mutant." FEBS Letters. 423. 129-132 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsukamoto,K.et al.: "Isolation and radiation hybrid mapying of dinuileotide polymorphism at the human estrogen receptor β loci" Journal of Human Genetics. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Ogawa,S.et al.: "The complote promary structure of human estrogen receptor beta (hER beta) and its helerodimerization nith ER alpha invivo and in vitro" Biochem.Biophys.Res.Commun.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Inoue,S.et al.: "A Novel RING finser protein,BFP,predominantly expressed in the brain." Biochem.Biophys.Res.Commun.240. 8-14 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mizunuma,H.et al.: "Estrogen receptor gene polymorphisims and bone minerel oensity of pre and postmenopansal women" Bore. 21. 379-383 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shiraki,M.et al.: "Association of bone mineral density with Apolipoprotein E Phenotype" J Bone Miner Res. 12. 1438-1445 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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