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Analysis of genetic abnormality in Hermansky-Pudlak syndrome with interstitial pneumonia.

Research Project

Project/Area Number 08457186
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionJuntendo University School of Medicine

Principal Investigator

TAMURA Naoaki  Juntendo Univ, Sch of Med, assist Professor, 医学部, 講師 (10188435)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Hideki  Juntendo Univ, Sch of Med, assistant Professor, 医学部, 講師 (90216747)
SETOGUCHI Yasuhiro  Juntendo Univ, Sch of Med, Clinical staff, 医学部, 助手 (90206649)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥4,200,000 (Direct Cost: ¥4,200,000)
KeywordsHPS-1 / pulmonary fibrosis / protein trafficking / gene polymorphism / AP-3 / HPS遺伝子 / PCR-SSCP / ヘルマンスキー・パドラック症候群 / 点突然変位
Research Abstract

The pathogenesis of idiopathic pulmonary fibrosis (IPF) is still unknown, however, significant correlation of risk of pulmonary fibrosis and genetic abnormality in patients with Hermansky-Pudlak syndrome (HPS) has been reported. HPS is an autosomal recessive disorder characterized by triad of oculocutaneous albinism, lysosomal lipofuscin storage and bleeding tendency. HPS is a rare disease but frequently observed in Puerto Rico and Swiss Alps. Almost 100 HPS patients have been reported in Japan. Most of HPS patients in Puerto Rico and Japan complicate pulmonary fibrosis and die until 5th decade, but not in Swiss. In this study, we have cloned HPS-responsible gene, HPS-1, which expands 30.5kb with 20 exons. More than 6 abnormal lesions in HPS-1 gene has been detected. Putative role of HPS-1 protein on protein trafficking has been proposed.
Sixteen bp duplication in exon 15, a most popular HPS-1 gene abnormality in Puerto Rico, represents higher risk of pulmonary fibrosis. However, none of analyzed Japanese UPS patients showed l6bp duplication in exon 15. Japanese HPS patients with pulmonary fibrosis were revealed to have gene polymorphism in exon 15, C to C point mutation resulting Pro49lArg substitution. Significant accumulation of this gene polymorphism was also observed in IPF (52%) in contrast to other several lung diseases and normals (p<O.OOOl). Furthermore, different pattern on the existence of this gene polymorphism between two pulmonary fibrosis, pulmonary fibrosis associated with connective tissue disease (11%, CTD-IP) and IPF (p<0.OOOl) was observed. This difference of genetic background between IPF and CTD-IP might relate to the pathogenetic difference of pulmonary fibrosis as well as different response to the therapy between two groups. This result suggests Pro49lArg substitution in HPS-1 gene might be a putative candidate of progenetic factor for and distinguish different mechanism of pulmonary fibrosis.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Oh, J, N.Tamura, et al: "Positional cloning of a genefor Hermansky-Pudlak syndrome" Natuve Genet.14. 300-306 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki K, N.Tamura, et al: "Prognostic value of Ia^+T lymphocytes in bronchoalveolar lavage fluid in pulmonary sarcoidosis." Am J Respir Crit.Cave Med. 154. 707-712 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tamura N, et al: "Alveolav macrophages produce the Env protein of an endogenous retrovirus, clone4-1, in interstitial lung diseases." Am J Respir. Cell Mol Biol.16. 429-437 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tamura, N, et al: "Syncytial cell formation in viro by type C retroviral particles in the lung of systemic lupus erythematosus." Clin.Exp.Immunol.107. 474-479 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oh, J, N.Tamura, et al: "Mutation amalysis of patients with Hermanslcy-Pudlak syndrome : a frameshift hot spot in the HPS gene and appavent locus heterogeneity." Am J.Hum.Genet.62. 593-598 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 木戸健治他: "Hermansky-Pudlak症候群 : 責任遺伝子と線維化肺" 現代医療. 31. 497-501 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oh J,et al.: "Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles." Nature Genet. 14. 300 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suzuki K,et al.: "Prognostic value of Ia^+ Tlymphocytes in bronchoalveolar lavage fluid in pulmonary sarcoidosis." Am J Respir Crit Care Med.154. 707-712 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tamura N,et al.: "Alveolar macrophages produce the Env protein of an endogenous retrovirus, clone 4-1, in interstitial lung diseases." Am J Respir Cell Mol Biol.16. 429-437 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tamura N,et al.: "Syncytial cell formation in vivo by type C retroviral particles in the lung of systemic lupus erythematosus." Clin Exp Immunol.107. 474-479 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oh J,et al.: "Mutation analysis of patients with Hermansky-Pudlak syndrome : a frameshift hot spot in the HPS gene and apparent locus heterogeneity" Am J Hum Genet. 62. 593 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tamura N.: "Hermansky-Pudlak syndrome." Mol Respiratology. 1. 253 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kido K,et al.: "Hermansky-Pudlak syndrome : a responsible gene and its role on pulmonary fibrosis." Gendiiryou.31. 497 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tamura N,et al.: "Accumulation of functionally impaired mitochondria and mitochondrial DNA deletion in human diaphragm." Am J Respir Crit Care Med.(submitted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oh.J., N.Tamura,et al: "Mutation analysis of patients with Hermansky-Pudlak syndrome : a frameshlft hot spot in the HPS gene and apparent locus hetaogenelty." Am.J.Hum.Genet.62. 593-598 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kitagawa H,Y.Setoguchi,et al: "DNA fragmentation and HSP72 gene expression by adensvirus mediated gene transfer in postischemic gerbil hippocompus and ventricle." Metab.Brain.Dis.13. 211-223 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 木戸健治 他: "Hermansky-Pudlak症候群:責任遺伝子と線維化肺" 現代医療. 31. 497-500 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Tamura,et al.: "Positional cloning of a gene for Hermansky-Pudlak syndrome,a disorder of cytoplasmic organeles" Nature Genetics. vol.14. 300-306 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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