Genetic Susceptibility to Asthma — Bronchial Hyperresponsiveness Coinherited with a Major Gene for Atopy

作者：Dirkje Sjoukje Postma, Eugene R. Bleecker, Pamela J. Amelung, Kenneth J. Holroyd, Jianfeng Xu, Carolien I. M. Panhuysen, Deborah A. Meyers, Roy C. Levitt · 发表于：New England Journal of Medicine · 年份：1995 · DOI：10.1056/nejm199510053331402 · 被引用次数：762 · 研究领域：Digestive system and related health、BRCA gene mutations in cancer、Asthma and respiratory diseases

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, P < 0.01) in pairs of siblings concordant for bronchial hyperresponsiveness (defined as a > or = 20 percent decrease in the forced expiratory volume in one second produced by histamine [threshold dose, < or = 16 mg per milliliter]), suggesting that these traits are coinherited. However, bronchial hyperresponsiveness was not correlated with serum IgE levels (r = 0....