Toll-Like Receptor 2 Gene Polymorphisms Associated with Aggressive Periodontitis in Japanese

Background and Objective: Aggressive periodontitis is a rare and very severe periodontal disease of early onset, which is closely associated with Porphyromonas. gingivalis (P.g.) infection in the Japanese population. TLR2 encodes Toll-like receptor 2, which plays an important role in the protective response to P.g. infection. We investigated a possible association between TLR2 and aggressive periodontitis. Material and Methods: Of 2,460 Japanese patients with periodontitis, 38 patients with aggressive periodontitis were enrolled in this study. These 38 aggressive periodontitis patients and 190 Japanese healthy controls were examined for an insertion/deletion (Ins/Del) polymorphism in exon 1, a polymorphism in intron 1 (rs7696323), and a synonymous polymorphism in exon 3 (rs3804100) in TLR2. Results: We found significant associations of resistance to aggressive periodontitis with the Ins allele (allele frequency in the patients versus controls, 0.540 vs. 0.676, OR=0.56, 95% confidence interval (CI); 0.34-0.92, p=0.022) and the T allele of rs3804100 (0.579 vs. 0.716, OR=0.55, 95% CI; 0.33-0.91, p=0.018), although the C allele of rs7696323 showed no significant association (0.733 vs. 0.829, OR=0.58). A permutation test of Ins/Del-rs7696323-rs3804100 haplotype revealed a significant association between Ins-C-T haplotype (0.252 vs. 0.479, p=0.0003) and resistance to aggressive periodontitis. Conclusions: The TLR2 polymorphisms were suggested to confer protection against aggressive periodontitis in a Japanese population. The association should be replicated in other cohorts to further identify the responsible TLR polymorphism(s) involved in the pathogenesis of aggressive periodontitis.