Multilocus models of polymorphic genes and their role in assessing the risk of chronic apical periodontitis: A prospective single-center case control study

Background. Chronic apical periodontitis is an inflammatory disease associated with infection of the root canal and represents a major challenge in dentistry. Its prevalence is rapidly increasing among the adult population. The condition is characterized by variability in inflammatory responses and bone resorption. Genetic factors play a central role in its pathogenesis. Single-nucleotide polymorphisms (SNPs) significantly affect gene expression and protein activity. Recent studies highlight the importance of integrating genetic data into clinical dentistry.

Objective. To determine the role of intergenic associations of key genes involved in the modulation of inflammatory and immune responses in hereditary predisposition to chronic apical periodontitis.

Methods. A prospective single-center case control study was conducted from November 2024 to April 2025 at the Yaroslavl State Medical University (Ministry of Health of the Russian Federation) and the Medical Center for Diagnostics and Prevention “Sodruzhestvo.” The study involved 200 participants: 150 patients with chronic apical periodontitis and 50 healthy controls. The diagnosis was confirmed clinically and radiographically. Single-nucleotide polymorphisms of eight genes (IL-10, IL-1β, TNF-α, GSTP1, CYP1A2, TP53, COL1A1, and MMP-9) were analyzed using real-time polymerase chain reaction (PCR). Statistical analysis was performed using JMP Pro v.18.0 (SAS Institute Inc., https://www.jmp.com, 2024), Haplostats v.1.9.7 (Schaid, D.J., & Sinnwell, J.P., Software for haplotype-based association analysis, USA), and MDR v.3.0.2 (Multifactor Dimensionality Reduction, SourceForge, USA). The optimal models were identified based on the highest cross-validation consistency (CVC) and lowest testing balanced accuracy error. The significance level was set at p < 0.05. Results. MDR analysis revealed significant intergenic interactions associated with the development of chronic apical periodontitis. The three-locus model IL-1β×TNF-α×MMP-9 demonstrated the highest predictive value (balanced accuracy 79.8%, cross-validation consistency 10/10), highlighting the synergistic effect of inflammatory cytokines and proteolytic processes. Hardy–Weinberg equilibrium analysis showed deviations for CYP1A2 and TP53 in the chronic apical periodontitis group, suggesting an influence of environmental factors. The Fruchterman—Reingold graph confirmed a strong interaction between IL-1β and TNF-α, whereas COL1A1 displayed a moderate association. These findings indicate the multigenic nature of predisposition to chronic apical periodontitis and enable personalized diagnostics and therapy based on the combined genetic effects.

Conclusion. The results of this study may lay a foundation for developing personalized diagnostic and treatment strategies that account for individual genetic profiles. Integrating such approaches into clinical practice could improve disease outcome prediction, optimize therapeutic interventions, and reduce the risk of complications related to the pathological process.

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