The nasal methylome and childhood atopic asthma.
Yang IV, Pedersen BS, Liu AH, O'Connor GT, Pillai D, Kattan M, Misiak RT, Gruchalla R, Szefler SJ, Khurana Hershey GK, Kercsmar C, Richards A, Stevens AD, Kolakowski CA, Makhija M, Sorkness CA, Krouse RZ, Visness C, Davidson EJ, Hennessy CE, Martin RJ, Togias A, Busse WW, and Schwartz DA. The nasal methylome and childhood atopic asthma. J Allergy Clin Immunol 2017; 139(5):1478-1488.
The Journal of allergy and clinical immunology
BACKGROUND: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma.
OBJECTIVE: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma.
METHODS: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36). Results were validated in an independent population of asthmatic children (n = 30) by using a shared healthy control population (n = 36) and in an independent population of white adult atopic asthmatic patients (n = 12) and control subjects (n = 12).
RESULTS: We identified 186 genes with significant methylation changes, differentially methylated regions or differentially methylated probes, after adjustment for age, sex, race/ethnicity, batch effects, inflation, and multiple comparisons. Genes differentially methylated included those with established roles in asthma and atopy and genes related to extracellular matrix, immunity, cell adhesion, epigenetic regulation, and airflow obstruction. The methylation changes were substantial (median, 9.5%; range, 2.6% to 29.5%). Hypomethylated and hypermethylated genes were associated with increased and decreased gene expression, respectively (P < 2.8 × 10
CONCLUSIONS: Epigenetic marks in respiratory epithelia are associated with allergic asthma and gene expression changes in inner-city children.
Medical Subject Headings
Adult; African Americans; Aged; Aged, 80 and over; Asthma; Child; DNA Methylation; Epigenesis, Genetic; European Continental Ancestry Group; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Nasal Mucosa; Young Adult