Impact of IL13 Genetic Polymorphism Arg130Gln on Total Serum IgE Levels and IFN-γ Gene Expression.

Summary This cross-sectional study was designed to investigate the extent of genetic susceptibility by targeting variants in IL-4/IL-13 signalling pathways leading to atopic disease in early childhood. We evaluated involvement of five single nucleotide polymorphisms IL4 C-590T, IL13 C-1055T, IL13 Arg130Gln, IL4RA Ile50Val and IL4RA Ser478Pro, in the control of serum total and antigen-specific IgE levels. Furthermore, we analyzed their association with changes in gene expression of five cytokines having key roles in inflammatory and anti-inflammatory immune response (IL-4, IL-13, IFN-γ, IL-8 and IL-10). Total and antigen-specific IgE levels in serum and gene expression of selected cytokines in peripheral blood were measured in 386 children aged 1 to 8 years. TaqMan allelic discrimination, ARMS-PCR and RFLP methods validated by sequencing were used for genotyping. All genotypes for children with total and antigen-specific IgE levels in the normal range were in Hardy-Weinberg equilibrium. Gene expression analyses were carried out using TaqMan Gene Expression Assays. We found elevated total IgE levels in carriers of IL13Arg130Gln variant allele (OR 1.84; 95% CI 1.16-2.93). This effect was more apparent for boys (OR 2.31; 95% CI 1.25-4.28). However, no significant association was observed for the other 4 variants examined. We found up-regulation of IFN-γ in children with elevated serum total IgE levels carrying Arg130 allele (P=0.005). No differences were found for IL4, IL8 or IL10 while IL13 gene expression was under detection limit. IL13 Arg130Gln genotypes can play a role in genetic susceptibility to allergy via regulation of serum total IgE levels and affecting IFN-γ gene expression. This article is protected by copyright. All rights reserved.