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Πέμπτη 20 Σεπτεμβρίου 2018

Identification of pathogenic genes and upstream regulators in allergic rhinitis

Publication date: Available online 19 September 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Yanhua Lei, Ping Guo, Jun An, Chao Guo, Fengxiang Lu, Minglei Liu

Abstract
Background

Allergic rhinitis (AR) is the main cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AR.

Methods

To screen pathogenic genes of AR, an integrated analysis was performed by using the microarray datasets in AR derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AR-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AR. Electronic validation was performed to verify the DEGs obtained by integrated analysis.

Results

From two GEO datasets obtained, we identified 793 DEGs (460 up-regulated and 333 down-regulated genes) between AR and normal control (NC). After GO and KEGG analysis, chronic inflammatory response and MAPK signaling pathway were significantly enriched pathways for DEGs. The expression of 6 genes (CLC, CST1, CRTAM, ILK, STAT1, and POSTN) was detected. The 6 genes in GEO: GSE51392 dataset played the same pattern with that in our integrated analysis.

Conclusions

The dysregulation of 3 genes (CST1, CLC and STAT1) may be involved in the pathogenesis of AR. AP-1 was associated with AR by regulating CST1 and CLC. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AR.



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