Gingival mRNA expression of two novel Y-linked epigenetic regulators during periodontal disease progression and its...

Despite the prevalence of periodontitis in males, the associated genetic and epigenetic factors remain unidentified. The study aimed to evaluate the expression of two novel Y-linked genes during periodontal disease progression and their biological significance through bioinformatic analysis.

USP9Y and KDM5D were identified from previous transcriptomic data as differentially expressed Y genes during periodontal disease progression. Gene Ontology and Reactome pathway enrichment analyses using the Enrichr database; protein-protein interactions using the STRING database; and network construction and Hub gene analysis in Cytoscape were performed. Gingival mRNA expression of USP9Y and KDM5D in healthy individuals and in patients with gingivitis, early, and advanced periodontitis was evaluated using Real-Time PCR (n=72).

USP9Y was significantly enriched in the cellular response to transforming growth factor beta stimulus, transmembrane receptor protein serine/threonine kinase, and bone morphogenetic protein signalling pathways. KDM5D is involved in histone lysine demethylation and the immune effector process. STRING analysis revealed interactions between USP9Y and KDM5D. The most relevant enriched biological process for USP9Y was the ubiquitin-dependent protein catabolic process. Both genes were among the top 10 hub genes and significantly enriched for Homologous to the E6-AP Carboxyl Terminus domain binding involved in epigenetic regulation. Statistically significant upregulation of both genes was observed during periodontal disease progression.

KDM5D and USP9Y are hub genes that play significant roles in regulating interconnected molecular pathways relevant to the inflammatory process in periodontitis. Significant differential expression of these novel Y-linked epigenetic regulators was observed during periodontal disease progression.