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2000 Fiscal Year Final Research Report Summary

Genetic Studies of Allergic Lung Diseases

Research Project

Project/Area Number 11670559
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

HIZAWA Nobuyuki  Hokkaido University Hospital, Instructor, 医学部・附属病院, 助手 (00301896)

Co-Investigator(Kenkyū-buntansha) YAMAGUCHI Etsuro  Hokkaido University Hospital, Assistant Professor, 医学部・附属病院, 講師 (10201831)
Project Period (FY) 1999 – 2000
KeywordsCCR2-64l / Total serum IgE levels / Sarcoidosis / FCER1B / CTLA4 / Th1 / Th1 balance
Research Abstract

We investigated the distribution of the CCR2-64l in 100 subjects with sarcoidosis and 122 healthy control subjects. The distribution of the CCR2-64l allele was significantly different between subjects with sarcoidosis and healthy control subjects. The presence of the CCR2-64l allele conferred a lower risk for the development of sarcoidosis. In addition, genetic factors are important in defining total serum IgE levels. A common -109C/T polymorphism at the promoter region of FCER1B was identified, although no variant was found in the entire coding region. Homozygosity for the 109T allele was associated with increased total serum IgE levels in 226 subjects with asthma. The gene encoding cytotoxic T lymphocyte antigen-4 (CTLA4) is another candidate responsible for high IgE responsiveness, because B7-CD28/CTLA-4 interaction can promote the differentiation and development of the Th2 lymphocyte subset. We performed a case-control study using 339 asthmatic patients and 305 healthy controls, which included 226 asthmatics and 219 healthy controls who had been previously studied for the -109C/T promoter polymorphism at FCER1B.Asthmatic patients who were homozygous for the -318C allele at the CTLA4 promoter region had higher levels of total serum IgE than those of patients carrying the -318T allele. The analysis of -318C/T and -109C/T promoter polymorphisms showed a significant correlation between the combined genotypes and increased levels of total IgE in asthmatic patients. Our findings represent genetic heterogeneity and complex interactions between genetic and environmental components involved in the regulation of sarcoidosis and total IgE levels, and support the theory that the Th1/Th1 balance in allergic lung diseases is determined by mutations in multiple genes each of which has a relatively small effect on the phenotype.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Hizawa N: "The role of the GC chemokine receptor 2 gene polymorphism"Am.J.Respir.Crit.Care Med.. 159・6. 2021-2023 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki I: "A new polymorphism in the 5' flanking region of the"Immunogenetics. 49・8. 738-739 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hizawa N: "A common FCER1B gene promoter polymorphism"Am.J.Respir.Crit.Care Med.. 161・3. 906-909 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki I: "Association between a Ct33T polymorphyem"Clin.Exp.Allergy. 30・12. 1746-1749 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hizawa N, Yamaguchi E, Furuya K, Jinushi J, Ito A, Kawakami Y.: "The role of the C-C chemokine receptor 2 gene polymorphism V64l (CCR2-64l) in sarcoidosis in a Japanese population."Am J Respir Crit Care Med. 159(6). 2021-3 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki I, Yamaguchi E, Hizawa N, Itoh A, Kawakami Y.: "A new polymorphism in the 5' flanking region of the human interleukin (IL)-4 gene."Immunogenetics. 49(7-8). 738-9 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hizawa N, Yamaguchi E, Jinushi E, Kawakami Y.: "A common FCER1B gene promoter polymorphism influences total serum IgE levels in a Japanese population."Am J Respir Crit Care Med.. 161(3 Pt 1). 906-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki I, N.Hizawa, E.Yamaguchi, Y.Kawakami: "Association between a C+33T polymorphism in the IL4 promoter region and total serum IgE levels."Clin Exp Allergy. 30(12). 1746-49 (2000)

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

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Published: 2002-03-26  

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