Genes for atopy and asthma

The genetic basis of atopic diseases is represented by a complex network of interacting genes or common genetic variants rather than a few disease-causing mutations. The individual risk of developing asthma or other atopic diseases is defined by the concert of interaction of these hereditary factors and environmental stimuli. The first decade of asthma genetics has been spent identifying those genetic regions through linkage analysis, which are likely to harbour asthma genes. At the same time, several candidate genes for asthma and atopy have been identified and their variants characterized, some of them even to a level of functional understanding. Rather than adding new candidate regions and genes to the pool of knowledge, the interest in the past year has moved to a more sophisticated statistical evaluation of the given linkage and association data and a more precise definition of so-called 'intermediate phenotypes'. Some of the results are quite surprising and have helped us to understand the underlying pathophysiology. For example, the distinct clinical traits of asthma, such as atopic sensitization or inflammation of the bronchial epithelium, seem to be defined by distinct subsets of predisposing genes. At the same time, the very same subsets of genes might underlie further clinical diseases with similar clinical features. Polymorphisms within IL-4R alpha, which had been shown to be associated with asthma and atopy, have also been shown to be associated with kidney allograft rejection, systemic lupus erythematosus and Crohn's disease. There might thus just be a few asthma and atopy genes. Finally, asthma and atopy genetics has now reached a point of practical application. The genetics of susceptibility to environmental stimuli, pharmacogenetic data, and the advent of new pharmaceutical targets will greatly influence the whole field of asthma and atopy. (C) 2001 Lippincott Williams & Wilkins.