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Study on genetic factors of airway hyperresponsiveness involved in pathogenesis of asthma

Research Project

Project/Area Number 08457184
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionIwate Medical University

Principal Investigator

INOUE Hiroshi  Iwate Medical University School of Medicine professor, 医学部, 教授 (40133962)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Hitoshi  Iwate Medical University School of Medicine associate professor, 医学部, 講師 (60215358)
YAMAUCHI Kohei  Iwate Medical University School of Medicine associate professor, 医学部, 助教授 (20200579)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥6,100,000 (Direct Cost: ¥6,100,000)
Keywordsbronchial asthma / airway hyperresponsiveness / genetic factor / histamine N-methyl-transferase / genetic polymorphyisim / 遺伝的素子 / ヒスタミンN-メチル基転移酵素 / Histamine N-methyltransferase (HMT) / 遺伝子多形 / ヒスタミン / MMT遺伝子 / アレルギー / CA繰り返し配列
Research Abstract

1. Polymorphism of HMT gene
To date, according to our previous report and the report by R Weishilboum, two changes of nucleotide sequence in coding region. Nucleotide 314 within codon 105 is a T or a C, resulting in codons that encode isoleucine or threonine. Nucleotide 595 within codon 199 is an A or a G, resulting isoleucine or vatine. In addition, we found clones which lack of 8 nuleotides (CTAACAAA) in ncleotide 89 of first exon. Furthermore CA repeat sequence near 6th exon was polymorphic and we analysed the niumber of CA repeat among 100 normal individuals. As a result, CA repeat number distributed from 15 to 30 and was thought to be a useful marker of polymorphism of MHT gene.
2. Genetic linckage of HMT gene to bronchial asthma
The airway hyperresponsiveness, a critical factor of bronchial asthma, has been recognized as one of physical characteristics inherited genetically. The level of HMT activity is closely associated with airway contractile response to histamine in guinea pigs (Nakazawa et al. , Am.J.Respir. Crit. Care Med. 1994, Hoshi et al. Am. J.Respir.Cell Mol. Biol. 1996). In this regard, to examine whether I-lIMIT gene is linked to bronchial asthma, we compared polymorphism of asthmatics to that of normal individuals. Aa a result, the distribution of CA repeat number was significantly different from that of normal individuals. Especially, CA repeat size smaller than 20 seemed to be a risk factor for bronchial asthma. Concerning the polymorphism influencing enzyme activity, HMT activity in the tissue of the individuals with 314T/C and 314T/T is lowerthan that with 314C/C.In this regard, we determined the pattern of 314 bases among 100 normal individuals and 100 asthmatics. As a result, because of small population of individuals with 314T/C (less than 10%), there was no significant difference between normals and asthma. To perform further analysis, we need to analyze the data on larger population of both normals and asthmatics.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] L-H Pan et al: "Co-expression of TNF-α and IL-IB in human aente pulmnoy fobootizdssensis" Pathology International. 46. 91-99 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] I ohno et al: "TGF-BI gene expresion by eosncphils in asthmatic airway inflamation" Am J Respir Cell Mol Biol. 14. 76-83 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Hoshi et al: "No_2 expostive increases airway contractor response to his tamine by decreasiry HMT activity in gunres pigs" Am J Reapir Cell Mol Biol. 15. 260-267 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Sano et al: "CD44 on blood eosimophls as movel marker of bronchiatasthmo management" Allengology International. 47. 29-35 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Maeda et al: "Induction of L-histidre decarboxylase in a human mast cell live, Hnc-1." Exp Hematol. 26. 325-331 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H Ueno et al: "Expression of human histrdne decarhoxy lose in Saccharinyes cereviside" J Biochem Mol Biol Biophys. 2. 141-146 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Pan, L-H., H.Ohitani, K.Yamauchi, and H.Nagura.: "Co-expression of TNF-alpha andIL-1beta in human acute pulmonary fibrotic diseases : An immunohistochemical analysis." Pathology International.46. 91-99 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohno I.Nitta Y.Yamauchi K.Hoshi H.Honma M.Woolley K.O'Byrne P.Tamura G.Jordana M.Shirato K.: "Transforming growth factor beta 1(TGF beta 1)gene expression by osinophils in asthmatic airway inflammation." Am J Respir Cell Mol Biol.15. 404-9 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshi, H., K.Yamauchi, K.Sekizawa, H.Iijima, E.Sakurai, K.Maeda, S.Okinaga, I.Ohno, M.Honma, G.Tamura, Y.Tanno, T.Watanabe, H.Sasaki and K.Shirato.: "Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs." Am J Respir Cell Mol Biol.14. 76-83 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Funayama T,Sekizawa K,Yamaya M,Yamauchi K,Ohno I,Ohrui T,Terajima M,Okinaga S,Sasaki H.: "Role of leukotriene degrading enzymes in pulmonary response to antigen infusion in the sensitized guinea pigs in vitro." Am J Respir Cell Mol Biol.15. 260-267 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohno I,Ohtani H,Nitta Y,Suzuki J.Hoshi H,Honma M,Isoyama S,Tanno Y,Tamura G,Yamauchi K,Nagura H,Shirato K.: "Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation." Am J Respir Cell Mol Biol.16. 212-219 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sano K,Yamauchi K,Hoshi H,Honma M,Tamura G,Shirato K.: "CD44 on blood eosinophils as a novel marker of bronchial asthma management." Allergology International. 47. 29-35 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Maeda K,Taniguchi H,Ohno I,Ohtsu H,Yamauchi K,Sakurai E,Tanno Y,Butterfield JH,Watanabe T,Shirato K: "Induction of L-histidine decarboxylase in a human mast cell line, HMC-1" Exp Hematol. 26. 325-331 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueno H,Kanai T,Atomi H,Ueda M,Tanaka A,Ohtsu H,Yamauch K,Watanabe T.: "Expression of human histidine decarboxylase in Saccharomyces cerevisiae." J Biochem Mol Biol Biophys.2. 141-146 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Maeda et al: "Induction of L-histidine decarboxylase in a human mastcell line,HMC-1." Exp Hematol. 26. 325-331 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.UENO et al: "Expression of human histidine decarboxylase in Saccharomyces cerensial" J.Biochem Mol Biol & Biophys. 2. 141-146 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Yamauchi et al: "Structure of hyman histamine N-methyltransferase gene" Am Respir Crit Care Med. 153. A226 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Hoshi et al: "NO_2 exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pig." Am J Respir Cell Mol Biol. 14. 76-83 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Funayama et al: "Role of leuko triene degrading enzymes in pulmonary response to antigen infusion in The sensitiged guinea pig in vitro" Am. J. Respir. Cell Mol Biol. 15. 260-267 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Yamauchi et al: "Polymorphism of histamine N-methyltransferase gene and its linkage to bronchial asthma." Am J. Respir Crit Cane Med. 155. A489 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] I.Ohno et al: "Eosinophils as a source of malvix metallo proteinase-9 in asthmatic airway inflammntion." Am J. Respir Cell Mol Biol. 16. 212-219 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Maeda et al: "Induction of L-histrdine decarboxylase in a human maet cell line, HMC-1." Exp Hematol.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Suzuki T: "Aerosolized Human Neutrophil Elastase Induces Arrway Constriction and Hyperespons heneus with pratection by Intravenous Pretreatment with Half length Secretory Lcukoproteuse Inhibitor" Am.J.Respir.Crot.Cane Med. 153. 1405-1411 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamauchi K: "strueture of human his tamine N-methyltransfeiase gevl" Am.J.Rcepir Crit.Cave Med. 153. A226 (1996)

    • Related Report
      1996 Annual Research Report

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

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