Genetics of food allergy

Abstract

Genetics of human diseases has passed through three main historical phases: (1) studies of formal genetics aimed at investigating mechanisms of inheritance using Mendelian models in population, family and twin surveys; (2) studies of associations between HLA antigens and diseases; and (3) direct mapping of genes through candidate gene or random genomic search approach. Very few data in each of these three phases are available for food allergy and intolerance. They are mostly confined to formal genetics studies of allergy in general and to HLA association studies in celiac diseases. The main reason for paucity of data in this important area of investigation is represented by the heterogeneity of the clinical entities grouped under the label of food allergy at the level of: (1) the clinical phenotype, because of the many diseases and end-organs interested; (2) pathophysiological variables involved, since several immunological and non-immunological mechanisms can be invoked in different cases of food allergy and intolerance; and (3) the foods or their absorbed metabolites which induce symptoms. However, progress made in genetics of allergy can be in part extrapolated to the limited number of cases where an IgE-mediated mechanism has been demonstrated. The review of studies based on a more punctual definition of the allergic phenotype and of the candidate genes (regions) of allergy: (1) suggests that allergen recognition and specific IgE response, total IgE (and IgG4) polyclonal activation, up-regulation of inflammatory cells (mast cells and eosinophils mainly) and hyper-responsiveness of end-organs are possibly regulated by different genetic and environmental factors; and (2) calls particular attention on the following genomic regions: 5q31.1–33, 6p21.3, 11q13,14. Research on genetics of food allergy and intolerance is highly recommended because of its high prevalence and of the potential applicative value of results for preventive measures of dietary control in subjects at risk. Since `food allergy and intolerance' does not represent an useful phenotype for genetic studies because of its heterogeneity, adequate strategies of gene mapping should be designed in study groups selected for defined variables with a well established role in the pathogenesis of the different clinical expressions of this common condition.