The role of gene-environment interactions in the development of food allergy

Abstract

The rates of IgE-mediated food allergy have increased globally, particularly in developed countries. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, suggesting that environmental exposures that alter the immune response play an important role. Genetic factors may also be used to predict an increased predisposition to these environmental risk factors, giving rise to the concept of gene-environment interactions, whereby differential risk of environmental exposures is mediated through the genome. Increasing evidence also suggests a role for epigenetic mechanisms, which are sensitive to environmental exposures, in the development of food allergy. This paper discusses the current state of knowledge regarding the environmental and genetic risk factors for food allergy and how environmental exposures may interact with immune genes to modify disease risk or outcome.

Keywords:

• environmental risk factors
• epigenetics
• food allergy
• gene-environment

Financial & competing interests disclosure

KJ Allen has received speakers honoraria from Danone, Nestle, Alphapharm and Aspen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Family history of allergic disease has been associated with increased risk of childhood food allergy.

• Maternal atopy may epigenetically program the risk for allergic disease during early fetal development.

• Epigenetic modifications are sensitive to environmental exposures, and thus represent a major mechanism underpinning environmentally mediated changes to gene expression.

• Altered DNA methylation in key immune genes has been associated with the development of clinical food allergy.

• As IgE-mediated food allergy and infantile eczema often co-exist, the role of FLG-LOF mutations in the development of food allergy has provided a useful line of candidate gene approach investigation. Mutations in genes predisposing to eczema may increase the risk of food allergy.

• Consumption of peanut-based food during pregnancy and in infancy has been associated with reduced risk of developing childhood peanut allergy.

• Vitamin D insufficiency during infancy has been associated with increased risk of food allergy. Whether this effect is also observed for maternal vitamin D deficiency is unclear.

• The rapidly growing prevalence of allergic disease cannot be explained in terms of traditional Mendelian inheritance, suggesting the causes are multi-factorial, and likely involve many genes in combination with lifestyle and environmental factors.