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

基因组 DNA 限制性片段长度多态性分析特应性和气道高反应性的研究。

基本信息

批准号：
04454248
负责人：
MUNAKATA Mitsuru
金额：
$ 4.29万
依托单位：
Hokkaido University, (School of Medicine, Internal Medicine I)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

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.

本研究首先对4个特应性哮喘家系进行了家系调查。本研究检测了皮肤点刺试验、IgE（RIST）、IgE（MAST）、乙酰甲胆碱和沙丁胺醇吸入气道反应性及外周血白细胞基因组DNA。特应性和吸入乙酰甲胆碱的气道反应的分布与自体显性遗传一致。对β 2-肾上腺素能受体（β 2-adrenergic receptor，Ban I）基因进行限制性片段长度多态性（restriction fragment length polymorphism，RFLP）分析。在日本人群中检测到β 2 ADR基因的两个等位基因多态性（等位基因2.3kb和2.1kb）。不携带2.3kb等位基因（2.1kb纯合子）的家系成员对沙丁胺醇的气道反应性显著低于携带2.3kb等位基因的家系成员。无2.3kb等位基因者哮喘发病率显著高于有2.3kb等位基因者。β 2 ADR基因RFLP与乙酰甲胆碱气道反应性和特应性状态无关。提示β_2 ADR基因Ban Ⅰ RFLP与β_2受体激动剂的气道反应性及支气管哮喘的发生可能有一定的关系虽然特应性的分离模式与常染色体显性遗传模式一致，特应性与11 q13位点无显著连锁。然而，携带0.96kb等位基因的受试者血清IgE水平显著高于不携带该等位基因的受试者。这些结果表明，虽然很难接受存在一个决定特应性表达的主基因，但似乎存在一个多基因决定特应性的基因。