Published Online: April 24, 2015
Exposure to indoor allergens in the home environment is known to exacerbate symptoms in children with asthma. One of the most common allergens associated with increased asthma severity is dust mite. However, there have been relatively few studies to determine how underlying genetic susceptibility may alter an asthmatic child’s response to dust mite exposure in the home. Most of the studies that examine these types of gene-environment interactions (G x E) focus on individual candidate genes, and may miss important interactions elsewhere in the genome. However, genome-wide scans for G x E include an overwhelming number of genes, making detection of an interaction effect difficult. In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), Sordillo and colleagues examine G x E in statistical models for severe asthma exacerbations, using immune cell responses to dust mite allergen to select the most biologically relevant genes to test for interaction with environmental dust mite exposure.
The authors of this study isolated peripheral blood mononuclear cells (PBMCs) from children and stimulated them with dust mite allergen (Der f 1). Genome-wide differential expression responses were determined for dust mite allergic vs. non-allergic subjects, identifying three genes (IL-9, IL-5 and PRG2) that were upregulated in those with dust mite allergy. In a population of asthmatic children, polymorphisms in these genes were tested for interaction with home exposure to dust mite, to alter their risk of a severe exacerbation (an Emergency Department Visit or hospitalization for asthma). The authors identified a potential interaction with a polymorphism in the IL-9 gene, suggesting that children who have the polymorphism, and who also have greater dust mite exposure, have the greatest risk of a severe exacerbation. For those children without the polymorphism, dust mite exposure mattered less.
In this study, the use of exposure-stimulated gene expression profiles allowed the authors to identify a novel gene target that may modify an asthmatic’s response to environmental dust mite allergen. This work by Sordillo et al suggests that asthmatic children with the IL-9 gene polymorphism may be most susceptible to dust mite allergen exposure in the home. Findings in this study also highlight the potential role of IL-9 in triggering a severe asthma exacerbation.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.