Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey
Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey
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DOI：
10.1111/jre.12533
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发表时间：
2018-06
影响因子：
3.5
通讯作者：
K. Tabeta;Michihiro Hosojima;Mayuka Nakajima;S. Miyauchi;H. Miyazawa;Naoki Takahashi;Y. Matsuda;N. Sugita;Y. Komatsu;Keisuke Sato;Tomomi Ishikawa;K. Akiishi;K. Yamazaki;Kiminori Kato;Akihiko Saito;Hiromasa Yoshie
中科院分区：
文献类型：
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作者：
K. Tabeta;Michihiro Hosojima;Mayuka Nakajima;S. Miyauchi;H. Miyazawa;Naoki Takahashi;Y. Matsuda;N. Sugita;Y. Komatsu;Keisuke Sato;Tomomi Ishikawa;K. Akiishi;K. Yamazaki;Kiminori Kato;Akihiko Saito;Hiromasa Yoshie
背景和证据先前的报道表明，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。这项初步研究的目的是调查，在日本的横断面社区调查，牙周炎的潜在血清生物标志物与ASVD和慢性牙周炎。材料与方法研究队列共包括108名男性受试者，他们每年进行健康检查。分析血清生物标志物（高敏C反应蛋白[hs-CRP]、前蛋白转化酶枯草杆菌蛋白酶/kexin 9型[PCSK 9]、白细胞介素-6、肿瘤坏死因子-α、可溶性CD 14、髓过氧化物酶、基质金属蛋白酶-3、脂联素、总胆红素[TBIL]和血脂），以确定其与牙周参数的相关性（如有）。采用臂踝主动脉脉搏波速度（PWV）指数和心踝血管指数（CAVI）评价主动脉僵硬度。结果与牙周健康受试者相比，牙周病受试者（确定为至少一个部位的探测深度≥4 mm）的PCSK 9和hs-CRP浓度升高（分别为P = .001和.042），TBIL浓度降低（P = .046）。与牙周健康受试者相比，牙周病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、残粒样胆固醇和氧化低密度脂蛋白的浓度升高（分别为P = 0.038、0.007、0.002和0.049）。多变量回归分析表明，囊袋深度≥4 mm的部位数量与PCSK 9浓度相关，与TBIL浓度独立负相关（标准化β = 0.243，P = 0.040;标准化β = -0.443，P = 0.0002;分别）。PCSK 9的受试者工作特征曲线分析表明，预测疾病部位存在的准确度中等（探测深度≥ 4 mm）（曲线下面积= 0.740）。牙周病患者与牙周健康者的PWV和CAVI值差异无统计学意义。结论在日本男性受试者中，血清PCSK 9和TBIL浓度与牙周参数相关。PCSK 9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导致ASVD的风险的潜力。有必要对更大人群进行纵向研究，以确认牙周炎与血清PCSK 9升高和TBIL降低的确切相关性。
BACKGROUND AND OBJECTIVES 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. MATERIAL AND METHODS 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). RESULTS 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. CONCLUSION 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.