A complete screening of the IL4 gene: novel polymorphisms and their association with asthma and IgE in childhood

BACKGROUND: IL-4, a cytokine with immunomodulatory functions, is involved in the upregulation of IgE production characteristic of asthma and allergy. Thus far, 2 single nucleotide polymorphisms (SNPs) in the promoter (C-589T) and 5' untranslated region (C-33T) of the IL4 gene have been identified. Polymorphism C-589T was reported to influence total serum IgE levels and bronchial hyperresponsiveness. However, no study has investigated the putative existence of further SNPs in exons, introns, and flanking regions of the IL4 gene. OBJECTIVE: A complete screening of the IL4 gene and its flanking regions for new polymorphisms was performed. Large-scale association studies in 1120 German schoolchildren were conducted to determine the effect of all polymorphisms present in the IL4 gene on the phenotypic expression of atopic diseases. METHODS: Denaturing HPLC and standard sequencing techniques were performed to detect novel polymorphisms in 33 unrelated subjects unselected for atopic diseases. Linkage disequilibrium was assessed for all polymorphisms in the IL4 gene, and association studies were performed. RESULTS: A total of 16 polymorphisms were identified in the IL4 gene, 14 of which were not reported previously. The pattern of linkage disequilibrium observed in IL4 could not be explained by physical distance. A significant association between a cluster of polymorphisms in strong linkage disequilibrium with each other and a physician's diagnosis of asthma and total serum IgE levels was found. CONCLUSION: These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE.