The role of genetics in food allergy

ABSTRACT

Introduction

As the prevalence of food allergies (FAs) increases worldwide, our understanding of their pathophysiology and risk factors is markedly expanding. In the past few decades, an increasing number of genes have been linked to FA. Identification of such genes may help in predicting the genetic risk for FA development, age of onset, clinical manifestation, causative allergen(s), and possibly the optimal treatment strategies. Furthermore, identification of these genetic factors can help to understand the complex interactions between genes and the environment in predisposition to FA.

Areas covered

We outline the recent important progress in determining genetic variants and disease-associated genes in IgE-mediated FA. We focused on the monogenic inborn errors of immunity (IEI) where FA is one of the clinical manifestations, emphasizing the genes and gene variants, which were linked to FA with some of the most robust evidence.

Expert opinion

Genetics play a significant role, either directly or along with environmental factors, in the development of FA. As a multifactorial disease, it is expected that multiple genes and genetic loci contribute to the risk for FA development. Identification of the involved genes should contribute to the area of FA regarding pathogenesis, prediction, recognition, prognosis, prevention, and possibly therapeutic interventions.

KEYWORDS:

• Allergy developments
• Allergy Genetics
• Food Allergy Development
• Food Allergy Genetics
• Food Allergy Risk
• Inborn Errors Of Immunity
• Peanut Allergy
• Primary immunodeficiency

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Article highlights

• Although the rapid increase in the prevalence of food allergy (FA) suggests that environmental factors, rather than the genetic background, provide greater contribution to its development, understanding the genetics of FA is important in determining risk factors, pathogenesis, and possible treatment options.

• Twin studies demonstrate that FA is highly heritable, and results from genome-wide association studies (GWASs) and candidate gene studies suggest significant association in the HLA-DR and -DQ region and genetic variants in several genes, such as FLG, the HLA locus, and FOXP3.

• Epigenetics may also play a role in the pathogenesis of FA. Studies showed differential DNA methylation in the genes involved in MAP kinase signaling including HLADQB1 gene or in the Treg-specific demethylated region (TSDR) of FOXP3 in various FAs. Differential DNA methylation may also play a role in resolution of FA.

• Monogenic diseases such as inborn errors of immunity (IEI) have elucidated pathways in the pathogenesis of FA. As expected, in IEIs that are associated with increased prevalence of FA, atopic dermatitis is a common clinical manifestation, which further tightens the link between the impaired skin barrier and food allergy.

• Interestingly, in autosomal dominant hyperIgE syndrome (AD-HIES) due to STAT3 deficiency, despite high prevalence of eczema, FA is not as common as in other IEIs that are associated with atopic dermatitis or in other children with atopic dermatitis. This observation emphasizes the role of STAT3 in mast cell development and function.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.