Bioinformatics analysis of candidate genes involved in ethanol-induced microtia pathogenesis based on a human genome...

Ethanol used by women during pregnancy increases the risk for microtia in the foetus. Traditionally, laboratory experiments and Mouse Genome Informatics (MGI) have been used to explore microtia pathogenesis. The aim of this study was to screen and verify hub genes involved in ethanol-induced microtia and to explore the potential molecular mechanisms.

Overlapping genes related to ethanol and microtia were acquired from the GeneCards database and filtered by confidence score. These genes were further analysed via bioinformatics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results were visualized with the clusterProfiler R package. A protein-protein interaction (PPI) network was constructed based on data from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database.

Overall, 41 genes related to both ethanol and microtia were identified. The genes most relevant to ethanol-induced microtia pathogenesis included FGFR-2, FGFR-3, FGF-8, TP53, IGF1, SHH, CTNNB1, and PAX6, among others. Most genes were strongly enriched for tissue and organ development in GO analysis. Additionally, many genes were enriched in the Ras, FoxO, MAPK, and PI3K-Akt signalling pathways in KEGG analysis.

Bioinformatics analysis was conducted on genes currently known to be related to ethanol-induced microtia pathogenesis. We propose that mechanisms involving FGF-family genes, TP53, IGF1 and SHH contribute significantly to ethanol-induced microtia and the accompanying malformation of other structures.