Atopy, airway responsiveness, and genes.

Asthma is a manifestation of bronchial hyperreactivity (BHR) and forms part of the spectrum of atopic disease. Some pedigree studies of atopy have suggested linkage with the high-affinity IgE receptor (FcE RI1) gene on chromosome 11q13, but others find no linkage. The molecular genetics of asthma and BHR have not been studied in the general population. We examined the genetic linkage of the Fce RIf gene with clinical asthma and the underlying phenotypes of BHR (to methacholine) and atopy (defined by skinprick testing) in 123 affected sibling-pairs recruited from the general population. We found evidence of significant linkage of a highly polymorphic microsatellite marker in the fifth intron of the FcE RI/, gene to a diagnosis of asthma (18.0% excess of shared alleles, P=0.002) and to BHR (21.7% excess of shared alleles, P= 0.00 1). Significant linkage was also observed in siblings sharing BHR when those with atopy were excluded (32.8% excess of shared alleles, P= 0.004). Atopy in the absence of BHR did not show significant linkage to the FcE RI, gene (7.2% excess of shared alleles, P= 0 124). These findings suggest that mutations in the FcE RIft gene or a closely linked gene influence the BHR underlying asthma, even in the absence of atopy. (Lancet 1995;346:1262-65)