Interest in Genomic study of Diabetes with Periodontitis

Abstract

Periodontitis is a complex inflammatory disease with well-established links to systemic conditions such as type 2 diabetes (T2D). The association of diabetes with periodontitis (PDDM) can cause very severe clinical complications. Our "in silico" study aims to identify the single nucleotide genetic polymorphism (SNPs) by comparing two groups of samples: patients with periodontitis (PD) and diabetic patients with periodontitis (PDDM), focusing on three genes: MCUR1, FOS and RAP2A in order to identify variants that may contribute to the pathogenesis and interactions of the disease. Variant identification was performed by the FreeBayes tool, followed by filtering and annotation using the SnpEff and SNPnexus tools. Group-specific SNPs were analyzed for functional impact using Combined Annotation Dependent Depletion (CADD) and FunSeq2 scores and then visualized via the UCSC Genome Browser. An enrichment analysis was performed with g:Profiler to explore the biological processes associated with each group. Our results revealed a significant number of non-coding regulatory variants with very high pathogenicity scores in PDDM patients. Notable results include the snip references: rs3810196 in MCUR1 (CADD: 15.68), rs1046117 in FOS (3′ UTR), and rs6115228 in RAP2A (CADD: 19.22), all exclusive to the PDDM group. Enrichment analysis showed that these PDDMspecific genes were associated with signal transduction, immune regulation, and metabolic stress, while PD-specific genes were linked to tissue remodeling processes and apoptosis. A transition/transversion ratio (Ts/Tv) of 2.22 confirmed the quality of the data. Our study was able to highlight distinct SNP profiles between PD and PDDM, suggesting that diabetes modifies the genetic landscape of periodontitis through increased regulatory variation. The variants identified in MCUR1, FOS and RAP2A contribute to a better understanding of the mechanisms involved in mitochondrial dysfunction., inflammatory signaling and immune dysregulation, and provide a basis for the future development of biomarkers and targeted therapeutic strategies