Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population

Abstract

Th2-dominated immune responses are believed to contribute to the athogenesis of atopic dermatitis (AD). IL-4 and IL-13 are typical pleiotropic Th2 cytokines that play a central role in IgE-dependent inflammatory reactions. Single-nucleotide polymorphisms (SNPs) in IL-4 and IL-13 have been reported in patients with allergic disease from numerous countries. Gene-gene interactions among genes have been identified in patients with asthma, although negative results have been reported. To investigate the associations of SNPs in these genes and the interactions between these genes in AD, we genotyped 23 SNPs of the IL-4, IL-13, IL-4R, IL-13R alpha 1 and IL-13R alpha 2 genes for 1089 case-control samples (631 AD patients and 458 controls) and analysed the SNPs and haplotypes in these genes. We also searched for gene-gene interactions among these five genes. Our data identified an association between rs3091307 and rs20541 in the IL-13 gene and between rs2265753 and rs2254672 in the IL-13R alpha 1 gene and the AD phenotype. In particular, three of the four SNPs were especially predictive of the allergic type of AD (ADe), and the haplotype TCGG in the IL-13R alpha 1 gene showed significant association with AD, especially ADe. Furthermore, the combination of rs3091307 GG/ rs2265753 GG (IL-13/IL-13R alpha 1) conveyed a significantly higher risk for developing ADe. However, we did not identify any SNPs in the IL-4, IL-4R and IL-13R alpha 2 genes that were associated with AD. As IL-13R alpha 1 is most likely expressed in Th17 cells rather than in Th2 cells, these data suggest diversity in the classification of Th cells that needs to be verified in future studies.