Abstract
BACKGROUND: The allergenicity of dust mite exposure might be dependent on variants in the gene for IL-10 (IL10). OBJECTIVES: To evaluate whether dust mite exposure modifies the effect of single nucleotide polymorphisms (SNPs) in IL10 on allergy and asthma exacerbations. METHODS: We genotyped 6 SNPs in IL10 in 417 Costa Rican children and 503 white children in the Childhood Asthma Management Program (CAMP) with asthma and their parents. We used family-based and population-based approaches to test for interactions between IL10 SNPs and dust mite allergen on serum IgE to dust mite in Costa Rica and on asthma exacerbations in Costa Rica and CAMP. RESULTS: Dust mite exposure significantly modified the relation between 3 SNPs in IL10 (rs1800896, rs3024492, and rs3024496) and IgE to dust mite in Costa Rica (P for interaction, .0004 for SNP rs1800896). For each of these SNPs, homozygosity for the minor allele was associated with increased levels of IgE to dust mite with increased dust mite exposure. Homozygosity for the minor allele of each of the 3 SNPs was associated with increased risk of occurrence (approximately 3-fold to 39-fold increase) and frequency of asthma exacerbations among children exposed to > or = 10 microg/g dust mite allergen in Costa Rica. Similar results were obtained for 2 of these SNPs (rs1800896 and rs3024496) among white children in CAMP. CONCLUSION: Our findings suggest that dust mite allergen levels modify the effect of IL10 SNPs on allergy and asthma exacerbations and may partly explain conflicting findings in this field.