Integrated Genome-wide Association and Single-cell Transcriptomic Analysis Identifies OAT as Therapeutic Targets for Periodontitis

Periodontitis is a chronic inflammatory disease affecting tooth-supporting tissues. Beyond microbial dysbiosis, host metabolic regulation plays a critical role. This study identified ornithine aminotransferase (OAT), a mitochondrial enzyme in amino acid metabolism, as associated with altered fibroblast phenotypes and metabolic profiles in periodontitis. Integrative genetic analysis showed a putative causal relationship between increased OAT expression and disease risk. Single-cell RNA-Seq revealed OAT enrichment in fibroblasts, especially in subsets with inflammatory and matrix-remodeling characteristics. In diseased tissues, OAT-positive fibroblasts exhibited heightened metabolic activity and acted as central nodes in intercellular communication with immune and endothelial cells. Pseudotime analysis indicated progressive downregulation of OAT during fibroblast differentiation. OAT expression correlated with activation of arginine and proline metabolism, implicating a role in sustaining inflammation and matrix degradation. These results suggest that OAT contributes to periodontal tissue damage and may serve as a therapeutic target.