Genetics in Asthma and Allergy

Major advances have occurred in the genetics of asthma and allergy, resulting in further understanding of the underlying pathophysiology of this disease. In this issue of the Immunology and Allergy Clinics of North America, the various approaches to these studies are discussed with presentation of current results. The first article, “Phenotype Definition, Age, and Gender in the Genetics of Asthma and Atopy” by Drs. Bottema, Reijmerink, Koppelman, Kerkhof, and Postma, discusses the critical role of phenotype and phenotype definition. Frequency and expression of these diseases are different in males versus females, which is also discussed in this article in relationship to the role of genetics and how sex differences may affect genetic studies and results.

The second article, “Family Studies and Positional Cloning of Genes for Asthma and Related Phenotypes” by Drs. Smith and Meyers, presents an overview of family studies and positionally cloned genes for asthma and related phenotypes. This article is followed by two articles that provide more detail on two different positionally cloned genes. The evolving story on the role of ADAM33 in asthma is presented by Drs. Holgate, Davies, Powell, and Holloway in the third article, “ADAM33: A Newly Identified Gene in the Pathogenesis of Asthma.” The fourth article, “HLA-G: An Asthma Gene on Chromosome 6p” by Dr. Ober, demonstrates the power of family studies in understanding the genetics of asthma and allergy.

Family studies are one approach to genetic studies; the other major approach is case–control studies (which may also be family-based), which are discussed in the fifth article, “Candidate Gene Association Studies and Evidence for Gene-by-Gene Interactions” by Michael Kabesch. Clearly, there are multiple susceptibility genes for common diseases such as asthma and allergy; therefore, it is important to test for gene-by-gene interactions as further discussed in this article. Just as there are multiple genes involved in common diseases, there are also strong environmental influences that need to be considered in genetics studies, which is addressed by Dr. Martinez in the sixth article, “Gene–Environment Interactions in Asthma and Allergy: A New Paradigm to Understand Disease Causation.”

An exciting and important area of genetics is pharmacogenetics (also a gene–environment [therapy] interaction), which is reviewed in the seventh article, “Asthma Pharmacogenomics” by Drs. Hawkins, Weiss, and Bleecker. The final article, “New Approaches to Understanding the Genetics of Asthma” by Dr. Meyers, discusses several new approaches that are being applied to studies on common diseases and are beginning to be applied to asthma and allergy. Together, these articles provide an overview on the important aspects of genetic studies on asthma and allergy and discussion of current results.