Toll‐like receptor‐1, ‐2, and ‐6 genotypes in relation to salivary human beta‐defensin‐1, ‐2, ‐3 and human neutrophilic peptide‐1

Abstract

Aim To examine whether functional gene polymorphisms of toll‐like receptor (TLR)1, TLR2, and TLR6 are related to the salivary concentrations of human beta‐defensins (hBDs)‐1, ‐2, ‐3, and human neutrophilic peptide (HNP)‐1. Materials and Methods Polymorphisms of TLR1 (rs5743618), TLR2 (rs5743708), and TLR6 (rs5743810) were genotyped by PCR‐based pyrosequencing from the salivary samples of 230 adults. Salivary hBD‐1, ‐2, ‐3, and HNP‐1 concentrations were measured using enzyme‐linked immunosorbent assay. General and periodontal health examinations, including panoramic radiography, were available for all participants. Results The genotype frequencies for wild types and variant types were as follows: 66.5% and 33.5% for TLR1, 95.5% and 4.5% for TLR2, and 25.1% and 74.9% for TLR6, respectively. The TLR2 heterozygote variant group exhibited higher salivary hBD‐2 concentrations than the TLR2 wild‐type group (p = .038). On the contrary, elevated hBD‐2 concentrations were detected in the TLR6 wild‐type group compared with the TLR6 heterozygote and homozygote variant group (p = .028). The associations between TLR6 genotypes and salivary hBD‐2 concentrations remained significant after adjusting them for periodontal status, age, and smoking. Conclusion hBD‐2 concentrations in saliva are related to TLR2 and TLR6 polymorphisms, but only the TLR6 genotype seems to exhibit an independent association with the salivary hBD‐2 concentrations.

Salivary Human β-Defensin 1-3 and Human α-Defensin-1 Levels in Relation to the Extent of Periodontal Disease and Tooth Loss in the Elderly

“…According to the present results, salivary HNP-1 levels elevate gradually with the increased number of pocket teeth. This finding of elevated HNP-1 levels in the periodontally diseased elderly is in line with our recent study on defensin levels in an adult population with an age range of 40-60 years [21]. A further comparison of defensin levels between the latter and present studies revealed that the levels of salivary HNP-1 in the Control group elderly were lower (median 33.4 pg/mL, range 0-329 pg/mL) than those in the adult population (median 81.9 pg/mL, range 17.4-184 pg/mL).…”

“…Based on the present study's results, hBD-2 levels are elevated in saliva where there is an increased extent of periodontitis; however, significant differences disappeared when p values were adjusted by the Bonferroni correction for multiple tests. In our recent study on salivary defensins in working-aged adults [21], the highest hBD-2 levels were measured in the localized periodontitis group (PPD ≥ 4 mm at 2-7 teeth), whereas the hBD-2 levels did not differ between the Control and the generalized periodontitis groups (no teeth vs. ≥14 teeth with PPD ≥ 4 mm). It is possible that the decreased hBD-2 levels with the expanded burden of the infection-induced inflammation are related to the enzymatic degradation of hBDs by host-derived and bacterial proteases.…”

“…In-house sandwich-ELISA assays (Rabbit anti-hBD-3, cat# 500-P241; Biotinylated rabbit anti-hBD-3, cat# 500-P241; hBD-3, cat# 300-52; Goat anti-HNP-1, cat#500-P126G; Biotinylated goat anti-hNP-1, cat# 500-P126G, and hNP-1, cat# 300-42; PeproTech ® ) were used in detections of salivary hBD-3 and HNP-1 levels. A detailed description of the ELISA assays is presented elsewhere [21].…”

Mass Spectrometry-Based Proteomics for Discovering Salivary Biomarkers in Periodontitis: A Systematic Review

“…Alterations in salivary neutrophil defensin levels have been associated with oral diseases such as squamous cell carcinoma, lichen planus, glossitis associated with iron deficiency, and mandibular osteomyelitis [102][103][104]. Regarding periodontitis, recent studies have found that the levels of neutrophil defensins in SWS increased progressively with rising numbers of pocketed teeth, which can be observed in both the adult population aged between 40-60 years [105] and the elderly population aged 65 years or more [106]. The consistent elevation of salivary neutrophil defensin in patients with CP suggests its potential utility as a biomarker for periodontitis diagnosis [107].…”

Salivary IL‐33 and sST2 levels in relation to TLR2 rs111200466 polymorphism and periodontitis

“…TLR2 activation can trigger the local release of IL‐33, which then activates ST2 receptors (Huang et al, 2020). TLR2 – 196 to −174 ins/del polymorphism has been shown to upregulate TLR2 expression in gastric and colorectal tissues (de Matos Lourenço et al, 2020; Proença et al, 2015), and TLR2 gene polymorphisms have the potential to change salivary immune‐regulating proteins (Gürsoy et al, 2022). Based on these prior studies, we expected that TLR2 rs111200466 polymorphism would alter salivary IL‐33 and sST2 levels, but this hypothesis was rejected.…”