Interleukin-4 receptor alpha gene variants and allergic disease

Several genome-wide screens have now been performed in different populations, looking for susceptibility genes for asthma and allergic disease. In general, the results of these genome screens have been somewhat disappointing in that, although chromosomal regions showing linkage have been identified, the strength of linkage at any given site has been inconsistent. These data suggest that a number of genes of moderate effect rather than a small number of genes with marked effects contribute to the genetic basis of allergic disease.To try to dissect out the important candidate genes that contribute to the risk of developing asthma or its important sub-phenotypes, several groups have concentrated on strong candidate genes that map to known susceptibility loci for asthma and atopy. Several such candidates have been identified (Table 1), including the gene for interleukin-4 receptor α (IL-4Rα), which is situated on chromosome 16p and is known to contain a number of polymorphisms. The recent paper from Carole Ober and colleagues [1] provides important information on the potential relevance of IL-4Rα gene variants in determining the risk of developing atopic disease.The IL-4Rα subunit forms part of the signalling complex for IL-4 itself but also serves as the α chain of the IL-13 receptor. Both IL-4 and IL-13 themselves have been implicated as potential candidate genes in the development of asthma, both being present in the TH2 cytokine locus on chromosome 5q23-31 [2]. Both IL-4 and IL-13 have overlapping functions, including mediating isotype switching to IgE synthesis.Several previous studies have suggested association and/or linkage between IL-4Rα gene variants and allergic disease, although not all studies have been positive. Mitsuyasu et al [3] reported the Ile50 allele of the IL-4Rα to be associated with atopic asthma, whereas Kruse et al [4] reported an association between the Pro478 and Arg551 alleles and low IgE levels. Hershey et al [5] reported an association bet