5. Genetics of hypersensitivity.

Genetics provides the basis for the host response to a variety of environmental factors that can play a role in the generation of complex genetic diseases, such as asthma and atopy. An understanding of the genetic bases for these conditions is therefore essential to understand their pathophysiology. Studies of the genetics of asthma and atopy have suffered from several daunting challenges. These include the recognition that these are conditions caused by numerous genes, with each gene assuming variable roles in different individuals. In addition, each gene presumably contributes only a small percentage to a given individual's genetic risk of asthma. This has led to the current situation, in which studies often demonstrate a lack of replication that can be explained by their being insufficiently powered. Furthermore, the pathophysiologies of asthma and atopy are incompletely understood, and the lack of clearly defined phenotypes also contributes to the inadequacies of the current literature. Nonetheless, regions of the human genome have been reproducibly associated with asthma and atopy. These regions have undergone intense study, and many genetic variants within them have been implicated as asthma and allergy genes. In addition, through candidate gene approaches, several genetic polymorphisms have been convincingly linked to increased risks for the development of asthma and atopy. Many of these genes are associated with alterations in responsiveness to therapeutic agents used in the treatment of these conditions. These genetic studies have an exciting potential for individually tailoring the therapeutic regimen to a given subject's genotype. It is to be hoped that they will also define new targets for the next generation of asthma and allergy therapeutic agents.