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

Publication date: Available online 4 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Erick Forno, Joanne Sordillo, John Brehm, Wei Chen, Takis Benos, Qi Yan, Lydiana Avila, Manuel Soto-Quirós, Michelle M. Cloutier, Angel Colón-Semidey, Maria Alvarez, Edna Acosta-Pérez, Scott T. Weiss, Augusto A. Litonjua, Glorisa Canino, Juan C. Celedón
BackgroundChildhood asthma is likely the result of gene-by-environment (GxE) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide GxE studies of dust mite allergen on asthma-related phenotypes.ObjectiveTo identify genetic variants whose effects on lung function in children with asthma are modified by level of dust mite allergen exposure.MethodsA genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (PRGOAL). Replication was attempted in two independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study.ResultsSNP rs117902240 showed a significant interaction with dust mite allergen level on FEV1 in PRGOAL (interaction P=3.1x10^-8), and replicated in the same direction in CAMP White children and CAMP Hispanic children (combined interaction P=0.0065 for replication cohorts and 7.4 x10^-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 CEBPβ, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1/FVC replicated in the independent cohorts.ConclusionsDust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1 in children with asthma. Analysis of existing data suggests this SNP may have transcription factor regulatory functions.Capsule SummaryDust mite allergen exposure modifies the effect of certain genetic polymorphisms on lung function in children with asthma.Clinical ImplicationsThe effect of certain genetic polymorphisms on lung function in children with asthma varies depending on their dust mite allergen exposure level. Future studies should assess whether personalized interventions for these children have a greater impact on lung function.



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