Gene-environment interactions in asthma and allergy: the end of the beginning?
OBJECTIVE
The pathogenesis of asthma and allergy typically involves not only distinct genetic and environmental factors, but also interactions between the two. Innate-immunity genes [particularly CD14, toll-like receptor (TLR)4 and TLR2, the critical mediators of responses to bacteria in the extracellular space] play a prominent role in gene-environment interactions relevant to asthma-related phenotypes because the interaction between microbial load and the innate-immune system is a critical determinant of both immune function and allergy/asthma susceptibility. This review presents recent findings illustrating the role of gene-environment interactions in asthma/allergy susceptibility.


RESULTS
Population studies have extended our understanding of the role of CD14 and innate-immune genes in the interplay between genetic variants and the environment, highlighting the complexity of these interactions and their significant influence on susceptibility to asthma and allergy.


CONCLUSIONS
Gene-environment interactions have become a leitmotiv in asthma and allergy genetics, especially over the last 3 years. The next challenge awaiting asthma and allergy geneticists will be to define the extent to which the search for gene-environment interactions can be successfully integrated with hypothesis-generating, genome-wide approaches aimed at the identification of genetic variants involved in the pathogenesis of complex-lung diseases.
Vercelli
Donata
D
Arizona Respiratory Center, Arizona Center for the Biology of Complex Diseases (ABCD), and Department of Cell Biology, College of Medicine, University of Arizona, Tucson, Arizona, USA. donata@arc.arizona.edu
D000818:Animals; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D004781:Environmental Exposure / Q000009:adverse effects*; D054884:Host-Pathogen Interactions; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
D018950:Lipopolysaccharide Receptors; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4