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 atop y have suggested linkage with the high-affinity IgE receptor (Fc epsil on RI beta) gene on chromosome 11q13, but others find no linkage. The molecular genetics of asthma and BHR have not been studied in the gene ral population. We examined the genetic linkage of the Fc epsilon RI b eta gene with clinical asthma and the underlying phenotypes of BHR (to methacholine) and atopy (defined by skinprick testing) in 123 affecte d sibling-pairs recruited from the general population. We found eviden ce of significant linkage of a highly polymorphic microsatellite marke r in the fifth intron of the Fc epsilon RI beta gene to a diagnosis of asthma (18.0% excess of shared alleles, P=0.002) and to BHR (21.7% ex cess of shared alleles, P=0.001). Significant linkage was also observe d in siblings sharing BHR when those with atopy were excluded (32.8% e xcess of shared alleles, P=0.004). Atopy in the absence of BHR did not show significant linkage to the Fc epsilon RI beta gene (72% excess o f shared alleles, P=0.124). These findings suggest that mutations in t he Fc epsilon RIP gene or a closely linked gene influence the BHR unde rlying asthma, even in the absence of atopy.