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

Abstract

Background 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. Objective To identify genetic variants whose effects on lung function in children with asthma are modified by level of dust mite allergen exposure. Methods A 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. Results SNP rs117902240 showed a significant interaction with dust mite allergen level on FEV1 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=0.0065 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 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. Conclusions Dust 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.

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“…Novel insights into how these responses occur following individual and combined exposures, and their associated health impacts, continue to emerge. Genetic polymorphisms also interact with many other environmental stressors to generate asthma phenotypes such as decreased lung function, adult‐onset asthma, or the severe asthma phenotype . Air pollution also induces transcriptomic, epigenomic, and metabolomic responses …”

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“…, and this past year, several studies expanded our knowledge of the influence of early-life allergen exposure on asthma risk and demonstrated interactions between these indoor allergens and genetic polymorphisms. 49,[53][54][55][56] These gene-environment interactions could act through epigenetic or nonepigenetic mechanisms. In addition, studies demonstrated links between genetic signatures and asthma phenotypes related to steroid responsiveness, adult-onset asthma, and total IgE levels.…”

“…The role played by the environment in shaping the development and exacerbation of asthma is examined as well (Fig 3). [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] We conclude with a section on health literacy, a critical component for successfully treating asthma, and other related advances.…”