Genetics of asthma.

As is becoming increasingly apparent, both atopy and asthma (however they are clinically defined) are a diverse group of related conditions, which are similarly disparate in their origins. Despite this, genetic factors are clearly operational. Speaking to their relatedness, linkages have been found between similar chromosomal sites for both atopy and asthma. Speaking to their divergence, there are also reports of the same phenotypes displaying linkage to different chromosomal areas. The likely explanation for this is that both the atopy and asthma phenotypes are polygenetic, requiring that multiple genes (some of them common to both) be expressed. For example, it may be that three genes, such as "a," "b," and "c," are involved in the development of skin test reactivity. Having only two of these genes, such as "a" and "b" or "b" and "c," alone does not result in the development of the defined phenotype of skin test reactivity. At the same time, it may be that to develop asthma one also needs three genes, such as "c", "d," and "e." One gene "c" involved in atopy inflammation is needed for both asthma and skin test reactivity. Genes "a" and "b" are also needed to be present for skin test reactivity, and a different set of genes, "d" and "e," are needed for asthma to develop. These genes "a" and "b" may be needed to localize the process in the skin and "d" and "e" to localize the process in the lung (Fig. 1). In addition to having the genetic predisposition for atopy and its associated conditions, environmental interactions are involved. Environmental conditions may be the initiating trigger and cause a shift in the balance between the protection and susceptibility of getting the clinical picture. In summary, atopy and asthma seem to be related conditions, involving both environmental and genetic factors, most likely consisting of multiple genes, which may interact with each other and the environment. A deeper [figure: see text] understanding of these genetic bases and the roles that environmental factors play in the development and manifestations of these conditions will provide better methods of diagnosis and treatment.