**3. Genetic associations of Th2-type cytokines with AD**

An initial linkage analysis in Amish families showed the association of 5q31.1 with serum IgE levels (21). This chromosome region contains a cluster of Th2-type cytokine genes. Therefore, much attention has been paid to the genetic association of Th2-type cytokine genes with atopy (defined as high serum IgE level) or with each specific phenotype of allergic diseases. As a result, several single nucleotide polymorphisms (SNPs) on the *IL4*, *IL5*, and *IL13* genes have been shown to be associated with atopy or AD (Table 2). Furthermore, SNPs located on the *IL4RA* and *IL13RA1* genes encoding the IL-4 receptor α chain (IL-4Rα) and the IL-13R α1 chain (IL-13Rα1) and on the *STAT6* gene encoding STAT6 were also reported to be associated with atopy or AD. IL-4Rα is a component of both type I IL-4R and type II IL-4R/IL-13, whereas IL-13Rα1 is a component of type II IL-4R/IL-13 (Figure 1). STAT6 is a transcriptional factor critical for IL-4 or IL-13 signals. The association of the *IL13*, *IL4RA*, and *STAT6* genes with IgE is confirmed by recent Genome Wide Association Studies (22, 23).


Table 2. Summary of genetic associations in Th2-type cytokines and their related molecules
