Do genetics play a role in the pathogenesis of asthma?

Abstract

Asthma is a phenotypically heterogeneous disorder associated with intermittent respiratory symptoms, bronchial hyperresponsiveness (BHR), and reversible airflow obstruction. 1, 2 Most individuals with asthma have evidence of BHR and atopy, with elevated total serum IgE, allergen-specific IgE, or skin-test reactivity to common allergens. At present, it is not clear whether asthma, BHR, and atopy are clinical manifestations of the same underlying primary defect or whether they share common pathways with distinct primary molecular origins. A genetic component to asthma has long been suggested by studies demonstrating increased prevalences of asthma among first-degree relatives of asthmatic subjects and greater concordance rates among monozygotic compared with dizygotic twins. 3-7 Such “clustering” in families is consistent with a genetic cause but may also reflect the effects of shared environmental exposures. Thus familial clustering does not prove a genetic cause. Although segregation analyses in populations of asthmatic families have suggested the likelihood of a major