GENETIC SUSCEPTIBILITY TO ASTHMA - BRONCHIAL, HYPERRESPONSIVENESS COINHERITED WITH A MAJOR GENE FOR ATOPY
GENETIC SUSCEPTIBILITY TO ASTHMA - BRONCHIAL, HYPERRESPONSIVENESS COINHERITED WITH A MAJOR GENE FOR ATOPY
复制标题
DOI：
10.1056/nejm199510053331402
复制
发表时间：
1995-10-05
影响因子：
158.5
通讯作者：
LEVITT, RC
中科院分区：
文献类型：
--
作者：
POSTMA, DS;BLEECKER, ER;LEVITT, RC
背景支气管高反应性是哮喘的一个危险因素，包括对各种刺激的支气管收缩反应增强。这种情况具有遗传性，与血清IgE水平和气道炎症密切相关。这些关系的基础是未知的，因为是遗传易感性的机制，支气管高反应性。我们试图确定特应性和支气管高反应性之间的相互关系，并调查这一组成部分的哮喘的染色体定位。我们研究了从荷兰同质人群中选出的84名哮喘先证者的303名子女和孙辈。测定通气功能、支气管对组胺的反应性和血清总IgE。评价了最后两个变量之间的关联。使用涉及对兄弟姐妹的分析，我们测试了支气管高反应性和染色体5 q31-q33上的遗传标记之间的联系，以前被证明与调节血清总IgE水平的遗传位点有关。血清总IgE水平呈强相关（r=0.65，P0.10）。对兄弟姐妹的分析表明，支气管高反应性与染色体5 q上的几个遗传标记连锁，包括D5 S436（P
Background. Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma.Methods. We studied 303 children and grandchildren of 84 probands with asthma selected from a homogeneous population in the Netherlands. Ventilatory function, bronchial responsiveness to histamine, and serum total IgE were measured. The association between the last two variables was evaluated. Using analyses involving pairs of siblings, we tested for linkage between bronchial hyperresponsiveness and genetic markers on chromosome 5q31-q33, previously shown to be linked to a genetic locus regulating serum total IgE levels.Results. Serum total IgE levels were strongly correlated (r=0.65, P0.10). Analyses of pairs of siblings showed linkage of bronchial hyperresponsiveness with several genetic markers on chromosome 5q, including D5S436 (P