The genetics of asthma.

In this paper we have summarized the evidence for a genetic contribution to asthma as well as the recent advances in techniques for identifying the location and function of genes that cause complex diseases. We have also reviewed how these techniques have been applied to the study of asthma and allergy. It is likely that rapid additional advances will be made over the next several years. There are ongoing genome-wide searches to identify additional genes. An understanding of the genetic variation that predisposes people to asthma and the atopic diseases could open a variety of potential diagnostic and therapeutic avenues. Firstly, the identification of the specific mutations that alter the immune response could provide targets for gene therapy. However, in the short run this is unlikely because the risks and costs associated with gene therapy do not presently justify application to alleviate the relatively nonlethal manifestations of allergic diseases. The second potential avenue will be in the development of specific pharmacologic therapy. For example, if variants of the IL-4 gene with enhanced function or of the IFN-gamma gene that have deficient function are identified as causative factors, drug development could be directed toward specific modulators of their effects. However, it is possible that redundancy in the immune and inflammatory responses, coupled with the likelihood of multiple gene involvement, will make such targeting fruitless or dangerous. The third consequence of identifying genetic variants predisposing to asthma and allergy is the possibility of screening. This is perhaps the most likely beneficial outcome of the present search for atopy genes. Recent studies suggest that the clinical onset of atopic diseases can be modified by preventing exposure to cigarette smoke and highly allergenic proteins in the first few years of life (188). At present the power of such studies is limited by the inability to predict those at risk with any certainty. Genetic screening of children born to atopic parents will allow more precise identification of those carrying atopy genes, and this could allow a focused attempt at environmental modification. In the short run this will allow the design of much more powerful prospective studies of prophylaxis, and in the long run screening may prove an effective strategy for asthma prevention.