Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness

Elevated serum Immunoglobulin E (IgE) levels and increased airway responsiv eness (AR) are correlated traits that are characteristic of asthma. It is n ot known to what extent these traits arise from distinct or shared genetic determinants. We investigated the genetic and environmental components of v ariance of serum total and specific IgE levels and AR in an Australian popu lation-based sample of 232 Caucasian nuclear families. The inter-relationsh ips of the genetic determinants of these traits were also investigated. Log , total serum IgE levels had a narrow-sense heritability (h(N)(2)) of 47.3% (SE = 10.0%). Specific serum IgE levels against house dust mite and timoth y grass, measured as a RAST Index, ad a h(N)(2) Of 33.8% (SE = 7.3%). AR, q uantified by the log, dose-response slope to methacholine (DRS), had a h(N) (2) of 30.0% (SE = 12.3%). Extended modeling demonstrated an approximate 70 % overlap in the genetic determinants of total and specific serum IgE level s. The genetic determinants of serum IgE levels and AR exhibited less than 30% sharing. These data are consistent with the existence of multiple genet ic determinants of the pathophysiologic traits associated with asthma, and suggest that AR is genetically distinct from atopy. These results have impl ications for gene discovery programs.