Résumé:
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
