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Genetic mapping of ossification of the posterior longitudinal ligament of the spine

Research Project

Project/Area Number 12671429
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKagoshima University

Principal Investigator

YONE Kazunori (2001-2002)  Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40182844)

古賀 公明 (2000)  鹿児島大学, 医学部, 助手 (20274821)

Co-Investigator(Kenkyū-buntansha) KOMIYA Setsuro  Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (30178371)
MATSUNAGA Shunji  Kagoshima University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (90229500)
HAYASHI Kyoji  Kagoshima University, University Hospital, Research Associate, 医学部附属病院, 助手 (50325784)
米 和徳  鹿児島大学, 医学部, 助教授 (40182844)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsOPLL / cDNA / BMP4 / 脊椎後縦靱帯 / 骨化 / 連鎖解析 / 罹患同胞対 / 11型コラーゲン / 脊椎後縦靭帯骨化症 / コラーゲン11A2 / 脊椎後縦靱帯骨化症
Research Abstract

Ossification of the posterior longitudinal ligament (OPLL) of the spine is the leading cause of myelopathy in Japan. To detect genetic determinants associated with OPLL, we performed an extensive nonparametric linkage study with 126 affected sib-pairs using markers for various candidate genes by distinct analyses, SIBPAL and GENEHUNTER. Eighty-eight candidate genes were selected by comparing the genes identified by complementary DNA (cDNA) microarray analysis of systematic gene expression profiles during osteoblastic differentiation of human mesenchymal stem cells with the genes known to be involved in bone metabolism. Of the 24 genes regulated during osteoblastic differentiation, only one, the alpha B crystalline gene, showed evidence of linkage (p = 0.016, nonparametric linkage [NPL] score = 1.83). Of 64 genes known to be associated with bone metabolism, 7 showed weak evidence of linkage by SIBPAL analysis (p < 0.05): cadherin 13 (CHD13), bone morphogenetic protein 4 (BMP4), proteoglycan 1 (PRG1), transforming growth factor beta 3 (TGFb3), osteopontin (OPN), parathyroid hormone receptor 1 (PTHR1), and insulin-like growth factor 1 (IGF1). Among these genes, BMP4 (NPL = 2.23), CDH13 (NPL = 2.00), TGFb3 ((NPL = 1.30), OPN (NPL = 1.15), and PTHR1 (NPL = 1.00) showed evidence of linkage by GENEHUNTER. Only BMP4 reached criteria of suggestive evidence of linkage. Because this gene is a well-known factor in osteogenetic function, BMP4 should be screened in further study for the polymorphism responsible.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Furushima K.: "Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine"J Bone Miner Res.. 17・1. 128-137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda S.: "Gender-specific haplotype association of collagen α2(XI)gene in ossification of the posterior longitudinal ligament of the spine"J Hum Genet.. 46・1. 1-4 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda S.: "Functional impact of human collagen α2(XI)gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine"J Bone Miner Res.. 16・5. 948-957 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakou T.: "Recent progress in the study of pathogenesis of ossification of the posterior longitudinal ligament"J Orthop Sci.. 5・3. 310-315 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Furushima K: "Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine"J Bone Miner Res. 17-1. 128-137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda S: "Gender-specific haplotype association of collagen α2(XI)gene in ossification of the posterior longitudinal ligament of the spine"J Hum Genet. 46-1. 1-4 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda S: "Functional impact of human collagen α2(XI)gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine"J Bone Miner Res. 16-5. 948-957 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakou T: "Recent Progress in the study of pathogenesis of ossification of the posterior longitudinal ligament"J Orthop Sci. 5-3. 310-315 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Horoaki Koga, et al.: "Large-Scale Screening for Candidate Genes of Ossification of the Posterior Longitudinal Ligament of the Spine"Journal of Bone and Mineral Research. 17(1). 128-137 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroaki Koga, et.al: "Gender-specific haplotype association of Collagen α2(XI) gene in ossification of the posterior longitudinal ligament of the spine."Journal of Human Genetics. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroaki Koga, et.al: "Functional Impact of Human Collagen (alpha) 2 (XI) Gene Polymorphism in Pathogenesis of Ossification of the Posterior Longitudinal Ligament of the spine."Journal of Bone and Mineral Research. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroaki Koga, et.al: "Recent progerss in the study of pathogenesis of ossification of the posterior longitudinal ligament."Journal of Orthopaedic Science. 5(3). 310-315 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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