The association of tumor necrosis factor alpha, lymphotoxin alpha, tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2 gene polymorphisms and serum levels with periodontitis and type 2 diabetes in Serbian population

Sanja Matic Petrovic; Nadja Nikolic; Bosko Toljic; Jelena Arambasic-Jovanovic; Biljana Milicic; Tanja Milicic; Aleksandra Jotic; Melita Vidakovic; Jelena Milasin; Ana Pucar

doi:10.1016/j.archoralbio.2020.104929

The association of tumor necrosis factor alpha, lymphotoxin alpha, tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2 gene polymorphisms and serum levels with periodontitis and type 2 diabetes in Serbian population

Arch Oral Biol. 2020 Dec:120:104929. doi: 10.1016/j.archoralbio.2020.104929. Epub 2020 Oct 7.

Authors

Affiliations

¹ Department of Oral Medicine and Periodontology, School of Dental Medicine, University of Belgrade, Dr Subotica 4, Belgrade, Serbia. Electronic address: [email protected].
² Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: [email protected].
³ Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: [email protected].
⁴ Department of Molecular Biology, Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: [email protected].
⁵ Department for Medical Statistics and Informatics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: [email protected].
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: [email protected].
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: [email protected].
⁸ Department of Molecular Biology, Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: [email protected].
⁹ Department of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 1, Belgrade, Serbia. Electronic address: [email protected].
¹⁰ Department of Oral Medicine and Periodontology, School of Dental Medicine, University of Belgrade, Dr Subotica 4, Belgrade, Serbia. Electronic address: [email protected].

PMID: 33091664
DOI: 10.1016/j.archoralbio.2020.104929

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.

Keywords: Periodontitis; Single nucleotide polymorphisms; Tumor necrosis factor - alpha; Tumor necrosis factor receptors; Type 2 diabetes mellitus.

MeSH terms

Case-Control Studies
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / genetics
Humans
Lymphotoxin-alpha* / blood
Lymphotoxin-alpha* / genetics
Periodontitis* / genetics
Polymorphism, Single Nucleotide
Receptors, Tumor Necrosis Factor, Type I* / blood
Receptors, Tumor Necrosis Factor, Type I* / genetics
Receptors, Tumor Necrosis Factor, Type II* / blood
Receptors, Tumor Necrosis Factor, Type II* / genetics
Serbia
Tumor Necrosis Factor-alpha* / blood
Tumor Necrosis Factor-alpha* / genetics

Substances

Lymphotoxin-alpha
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha