Study on Atopy and Airway Hyperrensponsiveness with Restriction Fragment Length Polymorphism Analysis of Genomic DNA.

点击翻译按钮获取中文摘要

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.