Inhibition of tumor necrosis factor receptor 1 and the risk of periodontitis

Zoheir Alayash; Sebastian-Edgar Baumeister; Birte Holtfreter; Thomas Kocher; Hansjörg Baurecht; Benjamin Ehmke; Stefan Lars Reckelkamm; Michael Nolde

doi:10.3389/fimmu.2023.1094175

Inhibition of tumor necrosis factor receptor 1 and the risk of periodontitis

Front Immunol. 2023 Feb 9:14:1094175. doi: 10.3389/fimmu.2023.1094175. eCollection 2023.

Authors

Zoheir Alayash¹, Sebastian-Edgar Baumeister¹, Birte Holtfreter², Thomas Kocher², Hansjörg Baurecht³, Benjamin Ehmke⁴, Stefan Lars Reckelkamm¹, Michael Nolde¹

Affiliations

¹ Institute of Health Services Research in Dentistry, University of Münster, Münster, Germany.
² Department of Restorative Dentistry, Periodontology, Endodontology, and Preventive and Pediatric Dentistry, University Medicine Greifswald, Greifswald, Germany.
³ Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
⁴ Clinic for Periodontology and Conservative Dentistry, University of Münster, Münster, Germany.

Abstract

Aim: To investigate the effect of genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) on the risk of periodontitis.

Materials and methods: Genetic instruments were selected from the vicinity of TNFR superfamily member 1A (TNFRSF1A) gene (chromosome 12; base pairs 6,437,923-6,451,280 as per GRCh37 assembly) based on their association with C-reactive protein (N= 575,531). Summary statistics of these variants were obtained from a genome-wide association study (GWAS) of 17,353 periodontitis cases and 28,210 controls to estimate the effect of TNFR1 inhibition on periodontitis using a fixed-effects inverse method.

Results: Considering rs1800693 as an instrument, we found no effect of TNFR1 inhibition on periodontitis risk (Odds ratio (OR) scaled per standard deviation increment in CRP: 1.57, 95% confidence interval (CI): 0.38;6.46). Similar results were derived from a secondary analysis that used three variants (rs767455, rs4149570, and rs4149577) to index TNFR1 inhibition.

Conclusions: We found no evidence of a potential efficacy of TNFR1 inhibition on periodontitis risk.

Keywords: cis-Mendelian randomization analysis; genetics; periodonditis; proinflammatory cytokine; tumor necrosis factor (TNF).

MeSH terms

Genome-Wide Association Study
Humans
Periodontitis* / genetics
Polymorphism, Single Nucleotide
Receptors, Tumor Necrosis Factor, Type I* / genetics

Substances

Receptors, Tumor Necrosis Factor, Type I