Gene-environment interactions in asthma and allergy: the end of the beginning?

PURPOSE OF REVIEW: 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.

RECENT FINDINGS: 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.

SUMMARY: 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.