Petrovic, Sanja Matic (56539393600)Sanja Matic (56539393600)PetrovicNikolic, Nadja (55324775800)Nadja (55324775800)NikolicToljic, Bosko (55927783800)Bosko (55927783800)ToljicArambasic-Jovanovic, Jelena (56812532600)Jelena (56812532600)Arambasic-JovanovicMilicic, Biljana (6603829143)Biljana (6603829143)MilicicMilicic, Tanja (24073432600)Tanja (24073432600)MilicicJotic, Aleksandra (13702545200)Aleksandra (13702545200)JoticVidakovic, Melita (6603600629)Melita (6603600629)VidakovicMilasin, Jelena (6603015594)Jelena (6603015594)MilasinPucar, Ana (24830760200)Ana (24830760200)Pucar2025-06-122025-06-122020https://doi.org/10.1016/j.archoralbio.2020.104929https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092640281&doi=10.1016%2fj.archoralbio.2020.104929&partnerID=40&md5=b3304e9528df0ac5ea5e892585bae0b1https://remedy.med.bg.ac.rs/handle/123456789/4584Objectives: Aiming to show that periodontitis (PD) and type 2 diabetes (T2D) are bidirectionally related and potentially linked by inflammatory cytokines, we searched for association between −308 G/A Tumor necrosis factor-alpha (TNFα), +252A/G Lymphotoxin-alpha (LTα), +36A/G Tumor necrosis factor receptor 1 (TNFR1) and +676 T/G tumor necrosis factor receptor 2 (TNFR2) single nucleotide polymorphisms (SNPs) and: risk of PD or PD + T2D; periodontitis parameters in PD and PD + T2D; serum levels of cytokines/their receptors. Relationship between periodontal inflammation and serum cytokine/receptor levels was also assessed. Design: Subjects were stratified as: 57 healthy controls (HC); 58 PD; 65 PD + T2D. Sociodemographic, environmental, behavioral and periodontal clinical data were recorded. SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism, while cytokines/receptors levels were quantified by enzyme-linked immunosorbent assay. Impact of periodontal inflammation was measured using periodontal inflamed surface area (PISA). Results: TNFα AA genotype showed protective effect in T2D + PD compared to PD, even adjusted for behavioral/environmental factors (OR 0.18; 95 %CI 0.037−0.886; p = 0.035). LTα AG heterozygotes had increased risk of PD (OR 3.27; 95 %CI 1.35−7.96; p = 0.016), while TNFR2 TG genotype had protective effect (OR = 0.44; 95 %CI 0.954−0.9794; p = 0.043). TNFR1 AA was predictor of periodontal pocket depth and clinical attachment loss in PD. Correlation between TNFR2 concentration and PISA was negative in PD, positive in PD + T2D. Conclusions: None of the SNPs showed cross-susceptibility between PD and T2D. + 252A/G LTα and +676 T/G TNFR2 SNPs are associated with PD risk. Periodontal destruction in healthy individuals is influenced by TNFR1 genotype. Impact of periodontal on systemic inflammation is masked by T2D. © 2020 Elsevier LtdPeriodontitisSingle nucleotide polymorphismsTumor necrosis factor - alphaTumor necrosis factor receptorsType 2 diabetes mellitus