Relationship between serum cotinine and risk of tooth loss in adults: A comprehensive statistical framework and molecular mechanisms

This study aimed to investigate the association between serum cotinine (a tobacco exposure biomarker) and tooth loss risk in adults. This study employed a statistical framework incorporating logistic regression, restricted cubic spline (RCS), machine learning, and web page construction to investigate the association between serum cotinine levels and tooth loss in 12,559 adult National Health and Nutrition Examination Survey participants. Network pharmacology was used to identify key targets, whereas molecular docking explored the specific mechanism of cotinine's impact on the target protein. Logistic regression and RCS demonstrated a positive (odds ratios = 1.106, 95% confidence interval: 1.085 to 1.127, p < 0.0001) and nonlinear (p for nonlinear < 0.0001) correlation between serum cotinine and tooth loss. After re-identifying 14 core genes via network pharmacology, molecular docking was employed to verify the specific protein molecular mechanism of cotinine's effect on tooth loss. Six different molecular docking methods were used to explain the specific molecular mechanism. The highest affinity of -7.3 kcal/mol was observed for the GSK3B-cotinine interaction. This study showed high serum cotinine levels strongly tied to greater tooth loss risk in adults, likely via core proteins controlling cell cycle and inflammation. Antioxidants partly reduced this risk, laying groundwork for early prevention and targeted treatments of tobacco-linked oral issues.