Diagnostic modulation of subgingival proteomic biomarkers by age and smoking habits in periodontitis

BACKGROUND: Although age and smoking influence the periodontal proteome, their impact on subgingival biomarkers for diagnosing periodontitis remains unclear. This multicenter study assessed their influence on subgingival proteins for disease detection. METHODS: Gingival crevicular fluid (GCF) samples were collected from 44 healthy subjects and 40 with periodontitis stages III-IV. Samples were analyzed using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Proteins were identified using UniProt, and diagnostic accuracy was evaluated using generalized additive models (GAM). Models included unadjusted proteins, proteins adjusted for age and smoking (years smoking and pack-year index), besides clinical variables alone. Three-fold cross-validation controlled overfitting. RESULTS: Age and smoking followed the expected epidemiological distribution, with most controls