*These authors contributed equally to this work.
A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2
Article first published online: 13 NOV 2009
© 2009 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 39, Issue 12, pages 1875–1888, December 2009
How to Cite
Genuneit, J., Cantelmo, J. L., Weinmayr, G., Wong, G. W. K., Cooper, P. J., Riikjärv, M.-A., Gotua, M., Kabesch, M., Von Mutius, E., Forastiere, F., Crane, J., Nystad, W., El-Sharif, N., Batlles-Garrido, J., García-Marcos, L., García-Hernández, G., Morales-Suarez-Varela, M., Nilsson, L., Bråbäck, L., Saraçlar, Y., Weiland, S. K., Cookson, W. O. C., Strachan, D., Moffatt, M. F. and the ISAAC Phase 2 Study Group (2009), A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2. Clinical & Experimental Allergy, 39: 1875–1888. doi: 10.1111/j.1365-2222.2009.03364.x
- Issue published online: 13 NOV 2009
- Article first published online: 13 NOV 2009
- Submitted 26 January 2009; revised 24 July 2009; accepted 28 July 2009
- candidate genes;
- multi-centre study
Background Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case–control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood.
Methods We compared 1105 wheezing and 3137 non-wheezing children aged 8–12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (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.
Results Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) 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.
Conclusions 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.