The role of the <em>STAT6</em> gene in the IL-4/IL-13 pathway: analyses of polymorphisms, functional studies and their effect on IgE regulation and the development of asthma.

Atopic diseases like asthma and allergies are characterized by an IgE-mediated immune response against common allergens. STAT6 is a key mediator in the activation of the IL-4/IL-13 pathway inducing the class-switch to IgE. Aim of the present work was to identify STAT6 polymorphisms which may influence the predisposition for atopic diseases in children. We demonstrated that C2892T in intron2 of STAT6 strongly contributes to the genetic control of IgE and the development of asthma, interacting also with other polymorphisms of the IL-4/IL-13 pathway. In vitro experiments revealed that intron2 is a silencer regulatory element. Yet, the existence of the polymorphic allele of C2892T increased STAT6 gene expression significantly compared to the wildtype allele. In addition, in vivo STAT6 expression was affected by the polymorphism C2892T. These effects seem to be due to binding of the transcription factor NF-kB only in the presence of the polymorphic T allele of SNP C2892T