Uncovering potential key genes associated with the pathogenesis of asthma: A microarray analysis of asthma-relevant tissues

Allergol Immunopathol (Madr). 2017 Mar-Apr;45(2):152-159. doi: 10.1016/j.aller.2016.08.007. Epub 2016 Nov 11.

Abstract

Background: The present study aimed to discover more potential genes associated with the pathogenesis of asthma.

Methods: The microarray data of GSE67940 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in bronchial alveolar lavage cells from patients with mild-moderate asthma (notSA) and severe asthma (SA) compared with normal controls (NC), respectively. Functional and pathway enrichment analysis, protein-protein interaction (PPI) network analysis were performed upon the identified up- and down-regulated DEGs. Besides, the gene association network based on the common up-regulated and down-regulated genes was generated and transcriptional regulatory pairs of overlapping DEGs in the PPI network were identified.

Results: A total of 104 DEGs (30 up- and 74 down-regulated genes) were identified in notSA vs. NC. Additionally, 2796 DEGs were screened out in SA vs. NC group, including 320 up-regulated DEGs, and 135 down-regulated DEGs. Specially, 41 overlapping DEGs were screened out in notSA vs. NC and SA vs. NC, including 16 common up-regulated genes and 25 common down-regulated genes. No pathways were enriched by the DEGs in notSA vs. NC. DEGs in SA vs. NC were associated with cytokine-cytokine receptor interaction. VEGFA was a hub protein in both the PPI networks of DEGs in notSA vs. NC and SA vs. NC. Gene association network showed that signalling pathways and cytokine-cytokine receptor interaction were involved in. The overlapping VEGFA, and IFRD1, and ZNF331 were regulated by more TFs.

Conclusion: Genes such as VEGFA, and IFRD1, and ZNF331 may be associated with pathogenesis of asthma.

Keywords: Asthma; Differentially expressed genes; Gene association network; Protein–protein interaction network; Transcription factors.

MeSH terms

  • Asthma / genetics*
  • Bronchoalveolar Lavage Fluid / cytology*
  • DNA-Binding Proteins / genetics*
  • Databases, Nucleic Acid
  • Disease Progression
  • Gene Regulatory Networks / immunology
  • Genetic Association Studies
  • Humans
  • Immediate-Early Proteins / genetics*
  • Immunity / genetics
  • Neoplasm Proteins / genetics*
  • Protein Interaction Domains and Motifs / genetics
  • Signal Transduction / genetics
  • Tissue Array Analysis / methods
  • Transcriptional Activation / genetics
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • DNA-Binding Proteins
  • IFRD1 protein, human
  • Immediate-Early Proteins
  • Neoplasm Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • ZNF331 protein, human