TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis

Area of Science:

• Genetics
• Immunology
• Periodontology

Background:

• Periodontitis involves genetic and environmental factors.
• Previous studies on Toll-like receptor 4 (TLR4) gene single nucleotide polymorphisms (SNPs) and periodontitis have been inconclusive.
• The interaction of TLR4 Asp299Gly SNP with smoking and Porphyromonas gingivalis in periodontitis is understudied.

Purpose of the Study:

• To examine the association between TLR4 Asp299Gly (rs4986790) and periodontitis and alveolar bone height loss (ABHL).
• To investigate interactions between the TLR4 SNP, smoking, and P. gingivalis prevalence.
• To use CD14/-260 SNP (rs2569190) as a control.

Main Methods:

• A multicenter study of 617 participants with rheumatoid arthritis or osteoarthritis.
• Periodontitis defined by CDC/AAP criteria; full-mouth examination and panoramic radiographs.
• TLR4 Asp299Gly and CD14/-260 SNPs genotyped using ImmunoChip; P. gingivalis detected by PCR.
• Multivariate logistic regression analyzed SNP associations and interactions with smoking and P. gingivalis.

Main Results:

• A significant negative interaction between TLR4 SNP and P. gingivalis regarding periodontitis (p=0.045).
• The TLR4 minor variant associated with less ABHL (OR=0.58; 95% CI: 0.36-0.95; p=0.029).
• No significant interaction between TLR4 SNP and smoking; CD14 SNP showed no association.

Conclusions:

• The TLR4 Asp299Gly SNP interacts with P. gingivalis, decreasing periodontitis risk.
• This TLR4 SNP may offer protection against ABHL.
• Targeting TLR4 signaling warrants investigation for periodontitis treatment, particularly when P. gingivalis is present.