Family based association analysis of the IL2 and IL15 genes in allergic disorders

Allergic diseases affect an increasing number of individuals and are a major global health problem. A substantial genetic contribution in the aetiology of allergic diseases is well documented. We have previously reported linkage of allergic diseases and atopy to the region harbouring the IL2 gene (4q27). IL15 is located approximately 20 Mb distal to IL2. The two genes encode cytokines that are structurally and functionally related, both inducing T-cell activation and proliferation. We screened the two genes for sequence variation and applied the seven single-nucleotide polymorphisms (SNPs) identified in a family based association study of two Danish samples comprising a total of 235 families with allergic diseases. None of the IL15 SNPs showed significant association and the haplotype analysis yielded inconsistent results in the two samples. In contrast, the two IL2 SNPs showed association both separately and in haplotypes with several atopic phenotypes, most significantly with IgE-mediated allergy. (single SNP P-value 0.0005 for positive skin prick test, haplotype P-value 0.019 for positive RAST test). To our knowledge, this is the first study reporting association between IL2 and IgE-mediated allergy, asthma and atopic eczema. The SNP (rs2069762) that showed the most consistent results is located in the promoter and has previously been shown to influence the level of IL2 expression. We suggest that the observed overtransmission of the T allele of this SNP may convey increased susceptibility to allergic disease by skewing the Th1/Th2 balance towards Th2.