Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children: The German Multicenter Atopy Study

Background: Among many published studies of specific IgE response or atopy, only a few showed positive marginal effects for 6 potentially functional single nucleotide polymorphisms (SNPs; C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene). SNPs were commonly considered individually, and therefore the true effect could be masked by other genes or environmental factors. Objective: We tested the relationship between these 6 SNPs and sensitization to food, mite, cat, and outdoor allergens in unrelated German children drawn from the Multicenter Atopy Study. Gene-gene and gene-environment interactions were also evaluated. Methods: Multiple logistic regression models were used for the analyses of 4 sensitization outcomes. Results: The variant C-1055T was significantly associated with increased risk of sensitization to food and outdoor allergens, with odds ratios of 3.49 (95% CI, 1.52-8.02) and 2.27 (95% CI, 1.04-4.94), respectively. The effects of the TT genotype on food sensitization appear to depend on variants in the IL4RA gene, in which marginally significant interaction terms were observed. Significant evidence supported an interaction between exposure to maternal smoking and variant Gln551Arg on risk of cat sensitization. In addition, we found that the effect of variant C-590T on sensitization to mite depended on Der p 1 allergen levels in carpet dust samples. Conclusions: These findings not only suggested that variants in the IL4, IL13, and IL4RA genes play an important role in controlling specific IgE response but also strengthened our understanding of gene-gene and gene-environment interaction on the development of specific sensitization in this study population.