Atopy and the human IL-4 receptor alpha chain

Background: Atopy is a common inherited disorder characterized by increased IgE responsiveness, but no functional analysis of the candidate genes rela ted to atopy has been performed. IL-4 is important for B-cell production of IgE, and the human IL-4 receptor a chain (hIL-4R alpha) is crucial for the binding and signal transduction of IL-4, so hIL-4R alpha may be a candidat e gene related to atopy. Objective: We examined the relationship between the variation at amino acid 50 of hIL-4R alpha and atopic asthma. Methods: We performed a genetic study to investigate the relationship betwe en the variation of amino acid 50 (isoleucine [Ile(50)] or valine [Val(50)] ) and atopic asthma in a Japanese population and a functional study with th e use of transfectants that expressed hIL4R alpha bearing either Ile(50) or Val(50). Furthermore, we analyzed CD23 expression and IgE synthesis after IL-4 stimulation of peripheral blood mononuclear cells bearing either Ile(5 0) or Val(50). Results: The prevalence of Ile(50) was higher than that of Val(50) in indiv iduals with atopic asthma, especially during childhood. In transfectants, g ermline epsilon transcription activity and Stat6 activity were upregulated by the Ile(50) variant, compared with Val(50), but receptor affinity for IL -4 was similar between the two. CD23 expression and IgE synthesis in respon se to IL-4 were augmented in Ile(50)-expressing peripheral mononuclear bloo d cells compared to cells expressing Val(50). Conclusion: The ILe(50) variant of hIL-4R alpha may be related to atopic as thma, particularly in children.