Food allergies affect approximately 6% of young children and 4% of adults in the United States. Clinical allergies, including food allergies, impact the quality of life of many individuals, with symptoms ranging from mild hives and vomiting to life threatening anaphylaxis. Multiple determinants, including genetic variation, environmental factors and gene-environment interactions, contribute to the development of allergies. While it is generally acknowledged that the risk for developing allergies is influenced by genetic factors, and numerous candidate genes have been associated with this increased risk, direct evidence supporting a role for these variants in the pathogenesis of food allergies has yet to be demonstrated. Immunoglobulin E (IgE) clearly plays a role in the development of allergies, including food allergies, in many individuals, and genes that play a role in switching the immunoglobulin produced by B cells to IgE are prominent in the list of genes identified in human genetic studies of allergy. This includes polymorphisms in the genes encoding the cytokines IL-4 and IL-13, as well as their receptor IL4RA and the downstream signaling molecule STAT6. More recent genome wide association studies have also implicated variants of the gene encoding the alpha-chain of the high affinity IgE receptor, FceR1, in determining serum IgE levels. In this application we test the function of these polymorphisms, examining their impact on FCER1A expression, total and allergen specific IgE and the response to food allergens using mouse models. Individuals, especially children, with food allergies often display high levels of IgE. Studies show that total serum IgE and allergen specific IgE levels are determined by both genetic and environmental factors. Recent studies have identified an important role for polymorphisms in the gene encoding the receptor for IgE in determining serum IgE levels. These studies also suggest that this polymorphism may impact the production of allergen specific IgE levels. We propose to test the role of these polymorphisms using mouse models of allergic disease, including a mouse model of peanut allergy.
Individuals, especially children, with food allergies often display high levels of IgE. Studies show that total serum IgE and allergen specific IgE levels are determined by both genetic and environmental factors. Recent studies have identified an important role for polymorphisms in the gene encoding the receptor for IgE in determining serum IgE levels. These studies also suggest that this polymorphism may impact the production of allergen specific IgE levels. We propose to test the role of these polymorphisms using mouse models of allergic disease, including a mouse model of peanut allergy.
