Genome-wide interaction study of dust mite allergen on lung function in children with asthma.

Abstract

Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV₁ with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10^-8), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10^-9 for all cohorts). Rs117902240 was positively associated with FEV₁ in children exposed to low dust mite allergen levels, but negatively associated with FEV₁ in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV₁/forced vital capacity replicated in the independent cohorts. Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV₁ in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions.