Atopic asthma after rhinovirus‐induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter

Abstract

Children with rhinovirus‐induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus‐associated atopic or nonatopic asthma, we analyzed a cohort of 5‐year‐old children (n = 45) according to the virus etiology of the first severe wheezing episode at the mean age of 13 months and to 5‐year asthma outcome. The development of atopic asthma in children with early rhinovirus‐induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8 years.

More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis

“…We confirmed these results, which may unriddle how asthmatic airway epithelial cells may be able to respond differently to the same stimuli as compared to healthy epithelial cells (280). First studies to investigate this effect in vivo are underway (291,292).…”

Epigenome‐wide association studies in asthma: A systematic review

“…Rhinovirus‐positive children aged 3‐23 months were recruited and followed until the age of four. The strongest association was annotated to SMAD3 gene for atopic asthma and to prostaglandin‐H2 D‐isomerase ( PTGDS ) gene for non‐atopic asthma . These changes were still present in an additional follow‐up at 8 years of age.…”

“…The strongest association was annotated to SMAD3 gene for atopic asthma and to prostaglandin-H2 D-isomerase (PTGDS) gene for non-atopic asthma. 49 These changes were still present in an additional follow-up at 8 years of age. However, the authors detected no changes in gene expression due to these differences.…”

“…A study by Lund et al in 2018 also examined epigenomic changes related to rhinovirus‐induced wheezing and their association with asthma in 48 children. Rhinovirus‐positive children aged 3‐23 months were recruited and followed until the age of four.…”

Highlights and recent developments in airway diseases in EAACI journals (2018)

“…In a separate study, DNA methylation in chromosomal regions previously linked to asthma has been demonstrated to increase the risk of children with rhinovirus-induced wheezing to develop asthma. 35 In a 10-year follow-up study, local AR has been demonstrated to be an independent rhinitis phenotype with a low rate of conversion to systemic atopy but significantly worsening throughout the years. 36 The epithelial barrier is the first line of defense against the external environment.…”