| Project/Area Number |
04454248
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Hokkaido University, (School of Medicine, Internal Medicine I) |
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Principal Investigator |
MUNAKATA Mitsuru HOKKAIDO UNIVERSITY, LECTURER, 医学部, 講師 (00209991)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Etsurou HOKKAIDO UMIVERSITY HOSPITAL, LECTURER, 医学部・附属病院, 講師 (10201831)
KAWAKAMI Yoshikazu HOKKAIDO UNIVERSITY, PROFESSOR, 医学部, 教授 (10001877)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Atopy / Bronchial asthma / Genetics / Immunoglobulin-E / Restriction fragment length polymorphism (RFLP) / Linkage analysis / Atopic gene / beta2-adrenergic receptor gene / Family study / 気道過放性 / 遺伝子解析 / 制限酵素断片長多型 / β_2受容性遺伝子 |
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| Research Abstract |
In this study, first, we performed family study in 4 families of the patients with atopic asthma. In this study, skin prick test, IgE(RIST), IgE(MAST), airway responese to inhaled methacholine and salbutamol were examined and genomic DNA was estacted from peripheral leukocytes. Distribution of atopy and airway responses to inhaled methacholine were consistent with auatosomal dominant inheritance. Distribution of airway responses to inhaled salbutamol was consistent with antosomal recessive inheritance.
For beta2-adrenergic receptor (B2ADR) gene, restriction fragment length polymorphism (RFLP) by Ban I digestion was examined. A two allele polymorphism (allele 2.3kb and 2.1kb) of the beta2ADR gene was detected in the Japanese population. Family members without allele 2.3kb (homozygote of allele 2.1kb) had significantly lower airway responses to inhaled salbutamol than those with allele 2.3kb. The incidence of asthmatics was significantly higher among those without allele 2.3kb than among those with allele 2.3kb. The beta2ADR gene RFLP had no relation to airway responses to methacholine and atopic state. These results suggest that Ban I RFLP of the beta2ADR gene may have some relation to the airway responses to the beta2-agonist and the incidence of bronchial asthma.
For atopic gene, RFLP detected by a DNA probe specific to chromosome 11q13 (lambda-MS51).Although segregation patterns of atopy were in agreement with the pattern of autosomal dominant inheritance, there was no significant linkage between atopy and locus 11q13. However, the subjects who have allele 0.96kb have significantly higher serum-IgE levels compared to those without it. These results suggest that, although it is difficult to accept the existence of a major gene that determine the expression of atopy, there seems to be one of the several genes which determine atopy polygenically.
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