COMPLEXITIES OF THE GENETICS OF ASTHMA

The task of deciphering the genetics of asthma is very complex. Recent studies of the familiar segregation of asthma showed that no single g ene accounts for a major part of the expression of the disease, and th at a polygenic model with some evidence of an oligogenic influence (i. e., a handful of loci being responsible for most of the genetic contro l) provided the best fit to the data. Although a final common pathway of recurrent bronchial obstruction is present in most cases of asthma, the disease shows marked phenotypic variability, suggesting etiologic heterogeneity and strong environmental influences. In an effort to ci rcumvent these obstacles, linkage studies for genes controlling for ap parently simpler phenotypes have been attempted. Total serum immunoglo bulin E (IgE) levels, for example, show strong familiar aggregation an d are known to be strongly correlated with asthma risk. Recent epidemi ologic studies have suggested, however, that the inherited component o f total serum IgE may be of little relevance as a determinant of asthm a. Sensitization to certain aeroallergens is also associated with incr eased prevalence of asthma and is likely to have a genetic component, but the aeroallergens involved vary markedly with locale. In addition, sensitization to aeroallergens occurring at an early age is more stro ngly associated with asthma risk than late allergic sensitization, sug gesting genetic heterogeneity. Therefore, studies of the genetics of p henotypes known to be strongly associated with asthma may clarify the causal role (if any) of the genes regulating their expression in the p athogenesis of asthma.