Sanja Matic Petrovic1, Nadja Nikolic2, Bosko Toljic3, Jelena Arambasic-Jovanovic4, Biljana Milicic5, Tanja Milicic6, Aleksandra Jotic7, Melita Vidakovic8, Jelena Milasin9, Ana Pucar10. 1. Department of Oral Medicine and Periodontology, School of Dental Medicine, University of Belgrade, Dr Subotica 4, Belgrade, Serbia. Electronic address: sanjamatic@gmail.com. 2. Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: nikolic.nadja@gmail.com. 3. Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: bosko.toljic@stomf.bg.ac.rs. 4. Department of Molecular Biology, Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: jelena.arambasic@ibiss.bg.ac.rs. 5. Department for Medical Statistics and Informatics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: biljana.milicic@stomf.bg.ac.rs. 6. Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, Belgrade, Serbia. Electronic address: icataca@gmail.com. 7. Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, Belgrade, Serbia. Electronic address: aleksandra.z.jotic@gmail.com. 8. Department of Molecular Biology, Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: melita@ibiss.bg.ac.rs. 9. Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: jelena.milasin@stomf.bg.ac.rs. 10. Department of Oral Medicine and Periodontology, School of Dental Medicine, University of Belgrade, Dr Subotica 4, Belgrade, Serbia. Electronic address: anapucar@gmail.com.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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/ATumor necrosis factor-alpha (TNFα), +252A/GLymphotoxin-alpha (LTα), +36A/G Tumor necrosis factor receptor 1 (TNFR1) and +676 T/Gtumor 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/GTNFR2 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.