Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.
Department of Clinical Nutrition Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Periodontal Res. 2018 Jun;53(3):446-456. doi: 10.1111/jre.12533. Epub 2018 Mar 8.
Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross-sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis.
The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high-sensitivity C-reactive protein [hs-CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin-6, tumor necrosis factor-α, soluble CD14, myeloperoxidase, matrix metalloproteinase-3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial-ankle aortic pulse wave velocity (PWV) index and the cardio-ankle vascular index (CAVI).
The concentrations of PCSK9 and hs-CRP were increased (P = .001 and .042, respectively), and the concentration of TBIL was decreased (P = .046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol and the concentrations of triglycerides, remnant-like particles-cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P = .038, .007, .002, and .049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized β = .243, P = .040; standardized β = -.443, P = .0002; respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects.
In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL.
先前的报告表明，几种血清生物标志物在细菌感染引起的牙周炎的发病机制、炎症反应和氧化应激中发挥作用，将慢性牙周炎与动脉粥样硬化性血管疾病（ASVD）联系起来。本初步研究的目的是在日本的一项横断面社区研究中，调查与 ASVD 和慢性牙周炎相关的潜在牙周炎血清生物标志物。
研究队列包括总共 108 名接受年度健康检查的男性受试者。分析了血清生物标志物（高敏 C 反应蛋白[hs-CRP]、前蛋白转化酶枯草溶菌素/克氏蛋白酶 9（PCSK9）、白细胞介素 6、肿瘤坏死因子-α、可溶性 CD14、髓过氧化物酶、基质金属蛋白酶 3、脂联素、总胆红素[TBIL]和血清脂质），以确定它们与牙周参数的关联（如果有）。使用肱踝动脉脉搏波速度（PWV）指数和心踝血管指数（CAVI）评估主动脉僵硬度。
与牙周健康受试者相比，患有牙周病（至少一个部位探诊深度≥4mm）的受试者的 PCSK9 和 hs-CRP 浓度升高（P=0.001 和 P=0.042），而 TBIL 浓度降低（P=0.046）。与牙周健康受试者相比，患有牙周病的受试者的低密度脂蛋白胆固醇（LDL-C）与高密度脂蛋白胆固醇的比值以及甘油三酯、残粒样颗粒胆固醇、氧化 LDL 的浓度升高（P=0.038、P=0.007、P=0.002 和 P=0.049）。多变量回归分析表明，牙周袋深度≥4mm的部位数量与 PCSK9 浓度独立相关，与 TBIL 浓度呈负相关（标准化β=0.243，P=0.040；标准化β=-0.443，P=0.0002）。PCSK9 的受试者工作特征曲线分析表明，其对预测疾病部位（探诊深度≥4mm）具有中等准确性（曲线下面积=0.740）。牙周病患者和牙周健康受试者的 PWV 和 CAVI 值无显著差异。
在日本男性受试者中，血清 PCSK9 和 TBIL 浓度与牙周参数相关。此外，PCSK9 可能是诊断慢性牙周炎的候选生物标志物，也可能具有评估牙周炎引起 ASVD 风险的潜力。需要对更大人群进行纵向研究，以确认牙周炎与血清 PCSK9 升高和 TBIL 降低的确切关联。
