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Publications

Journal Article Epublish

PubMed: 40723451 DOI: 10.3390/biology14070894

TLR4 Asp299Gly SNP (rs4986790) Protects from Periodontal Inflammatory Destruction by Altering TLR4 Susceptibility to LPS Stimulation.

Biology (Basel) 14(7)

Authors: Franco Cavalla, Claudia C Biguetti, Ariadne Letra, Renato M Silva, Alexandre R Vieira, Franz J Strauss, Gustavo P Garlet

Affiliations

  • School of Dentistry, University Andres Bello, Santiago 7590924, Chile.
  • Conservative Dentistry Department, University of Chile, Santiago 8820808, Chile.
  • Bauru School of Dentistry, University of Sao Paulo, Bauru 14040-902, Brazil.
  • Research Lab of Regenerative Medicine, The University of Texas Rio Grande Valley, Edinburg, TX 78539, USA.
  • Departments of Oral and Craniofacial Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15260, USA.
  • Departments of Oral and Craniofacial Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15260, USA. School of Dental Medicine, East Carolina University, Greenville, NC 27858, USA.
  • Clinic of Reconstructive Dentistry, Center of Dental Medicine, University of Zurich, 8006 Zurich, Switzerland. Health Sciences School, Universidad Autonoma de Chile, Santiago 7500912, Chile.

Abstract

Periodontitis is a multifactorial disease linked to host immune response and genetic predisposition. The TLR4 Asp299Gly single-nucleotide polymorphism (SNP, rs4986790) has been associated with altered responses to bacterial lipopolysaccharide (LPS) and may influence susceptibility to inflammatory diseases. Given the central role of TLR4 in innate immune recognition of periodontal pathogens, this study investigates the role of rs4986790 in modulating susceptibility to periodontal inflammatory destruction. A total of 1410 individuals from four populations were genotyped, with findings indicating a significant protective effect of the polymorphic allele. Functional assays demonstrated enhanced IL-8 secretion and increased sensitivity to CD14 inhibition in cells expressing the variant receptor. These results suggest that rs4986790 modifies the LPS response via TLR4, potentially offering protection against periodontal breakdown.

MeSH

Immunity, Periodontitis