Genetics of asthma: what do we need to know?

Establishing the contribution of genetics to the acquisition of asthma is likely to be essential in allowing fundamental questions regarding asthma etiology to be answered. Some topics that could be addressed include determination of different types of asthma, individuals who have the potential to become asthmatics, and the effect of environmental factors to cause asthma in genetically susceptible individuals. Epidemiological and immunological evidence has shown that there is an increased prevalence of asthma within families, and twin studies have shown greater concordance for asthma in monozygotic than dizygotic twins. Similar findings have been reported for IgE and IgE-related parameters. These observations strongly suggest a genetic component to asthma, but the strength of this influence has been difficult to ascertain due to the inevitable sharing of environment and genes in family studies. Recent work has focused on determining genes involved in asthma. Several genome searches have now been completed and regions in 16 of the 22 autosomal chromosomes have been associated with various asthma-related phenotypic factors, including total and specific IgE production, airway hyperresponsiveness, and symptoms of asthma. Polymorphisms associated with changes in phenotype have been described for several genes, including the genes for interleukin-4, tumor necrosis factor-alpha, the beta-chain of the high-affinity receptor for IgE, and the beta 2-adrenoreceptor. These findings indicate that the molecular genetics of asthma is highly complex and that much more work will be needed to allow the genetic susceptibility of asthma to be defined at the molecular level.