Asthma and IgE associated polymorphisms affect expression of TH17 genes

Abstract

T_H17 cells contribute to the pathogenesis of chronic inflammatory diseases such as asthma and T_H17 pathway tagging SNPs were associated with asthma and total serum IgE levels in childhood. In this study genotype-specific effects of these SNPs on the expression of T_H17 related molecules were analyzed in peripheral blood mononuclear cells (PBMCs) before and after allergen stimulation in 61 individuals. After correction for multiple testing, protein or mRNA expression levels of several molecules, including IL-17A, IL17-F, IL-23 and IL-23 receptor, were significantly correlated with asthma-associated SNPs (located in IL17F, IL22, IL23R and IL23A) and IgE-associated polymorphisms (located in IL17A and three SNPs in IL12B). Most extensive effects on T_H17 pathway expression were observed for the asthma-associated polymorphism IL17F rs7741835. In conclusion, genetic variants in IL17F and, to a smaller degree, IL17A and IL-23 signaling genes associated with asthma and IgE levels seem functional in influencing expression of T_H17 related molecules, indicating a contribution of these mechanisms to genetic susceptibility towards asthma and atopy.

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