Department of Orthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Department of Periodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Front Endocrinol (Lausanne). 2022 Aug 5;13:860274. doi: 10.3389/fendo.2022.860274. eCollection 2022.
The effect of hyperglycemia on periodontitis is mainly based on observational studies, and inconsistent results were found whether periodontal treatment favors glycemic control. The two-way relationship between periodontitis and hyperglycemia needs to be further elucidated. This study aims to evaluate the causal association of periodontitis with glycemic traits using bi-directional Mendelian randomization (MR) approach.
Summary statistics were sourced from large-scale genome-wide association study conducted for fasting glucose (N = 133,010), HbA1c (N = 123,665), type 2 diabetes (T2D, N = 659,316), and periodontitis (N = 506,594) among European ancestry. The causal relationship was estimated using the inverse-variance weighted (IVW) model and further validated through extensive complementary and sensitivity analyses.
Overall, IVW showed that a genetically higher level of fasting glucose was significantly associated with periodontitis (OR = 1.119; 95% CI = 1.045-1.197; = 0.007) after removing the outlying instruments. Such association was robust and consistent through other MR models. Limited evidence was found suggesting the association of HbA1C with periodontitis after excluding the outliers (IVW OR = 1.123; 95% CI = 1.026-1.229; = 0.048). These linkages remained statistically significant in multivariate MR analyses, after adjusting for body mass index. The reverse direction MR analyses did not exhibit the causal association of genetic liability to periodontitis with any of the glycemic trait tested.
Our MR study reaffirms previous findings and extends evidence to substantiate the causal effect of hyperglycemia on periodontitis. Future studies with robust genetic instruments are needed to confirm the causal association of periodontitis with glycemic traits.
高血糖对牙周炎的影响主要基于观察性研究，牙周治疗是否有利于血糖控制的结果并不一致。牙周炎和高血糖之间的双向关系需要进一步阐明。本研究旨在使用双向孟德尔随机化（MR）方法评估牙周炎与血糖特征之间的因果关系。
从大规模全基因组关联研究中获取空腹血糖（N=133010）、糖化血红蛋白（HbA1c，N=123665）、2 型糖尿病（T2D，N=659316）和牙周炎（N=506594）的汇总统计数据。使用逆方差加权（IVW）模型估计因果关系，并通过广泛的补充和敏感性分析进一步验证。
总体而言，IVW 表明，遗传水平较高的空腹血糖与牙周炎显著相关（OR=1.119；95%CI=1.045-1.197；=0.007），在去除异常值后。其他 MR 模型也证实了这种关联是稳健和一致的。在排除异常值后，发现 HbA1C 与牙周炎之间存在关联的证据有限（IVW OR=1.123；95%CI=1.026-1.229；=0.048）。在调整体重指数后，多变量 MR 分析中这些关联仍然具有统计学意义。反向 MR 分析并未显示遗传易感性与任何测试的血糖特征之间存在因果关系。
本 MR 研究再次证实了先前的发现，并提供了更多证据支持高血糖对牙周炎的因果影响。需要进行具有稳健遗传工具的未来研究来确认牙周炎与血糖特征之间的因果关系。
