Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

BackgroundCommon polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their genetic associations with asthma and allergy in a case−control sample from Phase Two of the International Study of Asthma and Allergies in Childhood. MethodsWe compared 1,105 wheezing and 3,137 non−wheezing children aged 8 to 12 years from 17 study centres in 13 countries. Genotyping of 55 candidate SNPs in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta−analysis. ResultsIn only four genes we detected significant associations with wheeze in the past year (p<0.05), with per allele odds ratios generally less than 1.3. Whereas variants in IL4R and TLR4 were also related with allergen specific IgE, polymorphisms in FCERIB and TLR9 were not. There were also highly significant associations between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. ConclusionsDespite the biological plausibility of IgE related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and raised IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had substantial power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema. This abstract is funded by: None.