Novel DNA Promoter Hypermethylation in Nasal Epithelium of Asthma

Abstract

Background: Abnormal epigenetic alterations influenced by external factors and affecting DNA expression contribute to the development of asthma. However, the role of the nasal epithelium in airway inflammation remains unknown.

Objective: The objective of this study is to identify novel DNA promoter hypermethylation, which suppresses mRNA expression in nasal epithelial of asthma.

Methods: Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Gene expression and DNA promoter methylation sites in key correlated modules between asthma and normal were identified by weighted gene co-expression network analysis. Gene Oncology and Kyoto Encyclopedia of Genes and Genomes were conducted to analyse the function of genes. Further validation was performed in human BEAS-2B cells challenged by IL-4 or IL-13.

Results: Lightcyan, lightgreen, midnightblue, cyan and tan modules in the mRNA expression dataset showed a close relationship with asthma, in which genes were enriched in TNF, IL-17, ErbB, MAPK and Estrogen signalling pathways. Blue and turquoise modules in the methylation profiling dataset were associated with asthma. Forty nine lowly expressed genes were identified to be correlated with aberrant DNA hypermethylation of promoters. Among these genes, the mRNA levels of <i>BCL10, GADD45B</i>, <i>LSR</i> and </i>SQSTM1</i> were downregulated in BEAS-2B cells challenged with IL-4 or IL-13.

Conclusion: Four potential genes in the nasal epithelium, by hypermethylating their own DNA promoter, might mediate the inflammatory response in the pathogenesis of asthma. Analyzing epigenomic data by integrated bioinformatics helps to understand the role of DNA methylation in asthma, with the goal of providing new perspectives for diagnosis and therapy.

Keywords: Asthma; WGCNA; hypermethylation; methylome; nasal epithelium; transcriptome.