MiR-107 and Its Association With House Dust Mite Sensitisation: Implications for Asthma.

Abstract

MicroRNAs (miRNAs) have been linked to allergic diseases but their effects on sensitisation to allergens in individuals with asthma are unknown. We aimed to identify miRNAs associated with house dust mite (HDM) sensitisation in childhood asthma. Serum samples from 1126 children with asthma who participated in the Genetics of Asthma in Costa Rica Study (GACRS) were profiled for 304 miRNAs. We first divided according to HDM sensitisation and then tested whether miRNAs were differentially expressed (DE) between the two groups. Gene enrichment analysis for target genes of the DE miRNAs was then performed to identify potential causal pathways. Replication analysis was performed in the Childhood Asthma Management Program (CAMP), in which expression data of 258 miRNAs in 491 children were available. A mediation analysis was conducted to discern relationships between miRNA and phenotype differences according to HDM sensitisation in GACRS cohort. There were 906 (80.5%) and 220 (19.5%) subjects in the GACRS HDM+ and HDM- groups. Compared with HDM- participants, those in the HDM+ group were more likely to be severe in variables including pulmonary function, oral corticosteroid use and blood tests. A total of 17 miRNAs were DE (p < 0.05) between the two groups, with miR-642a-3p, let-7c-5p and miR-107 most significantly associated with HDM sensitisation. In CAMP, there were 39 DE miRNAs, and increased expression of miR-107 in HDM+ children was replicated in this cohort. In both GACRS and CAMP, the cadherin-binding pathway was enriched in an analysis of target genes for DE miRNA. In a mediation analysis, miR-107 showed significant indirect effects on eosinophil count and total IgE that were mediated by HDM sensitisation. In children with asthma, miR-107 is associated with HDM sensitisation. Furthermore, miR-107 was indirectly associated with total IgE and eosinophil count through HDM sensitisation.