GENETICS OF FOOD ALLERGY

Genetics of human diseases has passed through three main historical ph ases: (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 gen omic search approach. Very few data in each of these three phases are available for food allergy and intolerance. They are mostly confined t o formal genetics studies of allergy in general and to HLA association studies in celiac diseases. The main reason for paucity of data in th is important area of investigation is represented by the heterogeneity of the clinical entities grouped under the label of food allergy at t he 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 in voked in different cases of food allergy and intolerance; and (3) the foods or their absorbed metabolites which induce symptoms. However, pr ogress made in genetics of allergy can be in part extrapolated to the limited number of cases where an IgE-mediated mechanism has been demon strated. 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, to tal IgE (and IgG4) polyclonal activation, up-regulation of inflammator y cells (mast cells and eosinophils mainly) and hyper-responsiveness o f end-organs are possibly regulated by different genetic and environme ntal factors; and (2) calls particular attention on the following geno mic regions: 5q 31.1-33, 6p 21.3, 11q 13, 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 prev entive measures of dietary control in subjects at risk. Since 'food al lergy and intolerance' does not represent an useful phenotype for gene tic studies because of its heterogeneity, adequate strategies of gene mapping should be designed in study groups selected for defined variab les with a well established role in the pathogenesis of the different clinical expressions of this common condition. (C) 1997 Elsevier Scien ce B.V.