Filaggrin Loss-of-Function Mutations Are Risk Factors for Severe Food Allergy in Children with Atopic Dermatitis

Abstract

Atopic dermatitis is frequently associated with the onset of other allergic conditions, such as asthma, rhino-conjunctivitis and food allergy. The etiology of atopic dermatitis is marginally understood in spite of the number of predisposing factors, above all, mutations in the Filaggrin gene (FLG). In this study, the association between loss-of-function variants in the FLG gene and other allergic manifestations, in particular food allergy, was evaluated in an Italian pediatric population affected by atopic dermatitis. The 10 more frequently mutated loci in the FLG gene were genotyped in 238 children affected by atopic dermatitis and tested for association with clinical features of allergic disorders by a multivariate logistic regression model. R501X and 2282del4 were the only two mutations identified; 12.2% of children carry one of these variants, corresponding to an allelic frequency of 6.5%. According to multivariate statistical analysis, loss-of-function variants in the FLG gene represent a risk factor for the onset of severe manifestations of food allergy (OR = 8.9; CI: 3.1-28.3). Peanut and hazelnut were identified as high-risk foods in patients with FLG mutations. This study demonstrates that atopic children carrying FLG mutations represent a high-risk population due to their predisposition to develop severe food allergy reactions, such as anaphylaxis.

Keywords: Filaggrin; atopic dermatitis; food allergy.

Figure 1

Structure of the coding portion of FLG gene. The main part of the protein is encoded by the third and larger exon, having a highly complex and repetitive structure with 10–12 near-identical tandem repeats (RPT). The analyzed loss-of-function variants of the FLG gene are reported.

Figure 2

Food specific IgE levels in the FLG mutated (grey) and wild-type (white) groups. Geometric IgE mean values with standard error are reported. Hazelnut (*, p-value = 0.03) is the only variable with a statistically significant difference between the FLG mutated and wild-type groups according to the multivariate model.