Yan Jiawu, Zheng Wenxuan, Xie Shixin, Yun Xiao, Wang Zhongyuan, Zhou Hanyu
Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China; Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Int Dent J. 2025 Apr;75(2):707-715. doi: 10.1016/j.identj.2024.10.018. Epub 2024 Dec 10.
Observational studies suggest an association between metabolic syndrome (MetS) and periodontitis. However, observational studies are susceptible to reverse causation and confounding factors, so the causality of this association is uncertain. Causal association between compounds of MetS and periodontitis has been well studied. Using Mendelian randomisation (MR), we aimed to comprehensively evaluate the bidirectional relationship between MetS as a whole and periodontitis and provide clinical insight.
We used genetic instruments from the most comprehensive genome-wide association studies of European descent for MetS (n = 291,107) as well as periodontitis from both the FinnGen consortium (n = 195,395) and GeneLifestyle Interactions in Dental Endpoints (GLIDE, n = 45,563) consortium to investigate the causal relationship between MetS and periodontitis and vice versa. We used the inverse-variance weighted (IVW) method to derive the primary causal estimates and evaluated the robustness of our results with a series of sensitivity analyses.
MR analysis based on FinnGen consortium indicated a negative causal association of MetS on periodontitis (OR = 0.882, 95% CI = 0.791-0.983, P = .023), while MR analysis based on GLIDE consortium did not support a causal relation of MetS on periodontitis (OR = 0.986, 95% CI = 0.920-1.057, P = .697). These results were consistent after adjusting for potential confounding factors by multivariable MR analyses. Results from meta analysis did not support a causal association of MetS on periodontitis. Sensitivity analysis showed that there was no existence of pleiotropy. In the reverse direction, periodontitis showed no association with MetS.
Within the scope of this MR study, MetS and periodontitis are not causally related.
Further studies are needed to clarify the underlying mechanism between metabolic syndrome and periodontitis.
观察性研究表明代谢综合征（MetS）与牙周炎之间存在关联。然而，观察性研究容易受到反向因果关系和混杂因素的影响，因此这种关联的因果关系尚不确定。对代谢综合征各成分与牙周炎之间的因果关联已有充分研究。我们旨在通过孟德尔随机化（MR）全面评估整体代谢综合征与牙周炎之间的双向关系，并提供临床见解。
我们使用了来自欧洲血统人群最全面的全基因组关联研究的遗传工具，其中代谢综合征的样本量为291,107例，牙周炎的样本量来自芬兰基因联盟（FinnGen consortium，n = 195,395）和牙科终点基因与生活方式相互作用研究（GLIDE，n = 45,563）联盟，以研究代谢综合征与牙周炎之间的因果关系，反之亦然。我们使用逆方差加权（IVW）方法得出主要因果估计值，并通过一系列敏感性分析评估结果的稳健性。
基于芬兰基因联盟的MR分析表明代谢综合征对牙周炎存在负向因果关联（OR = 0.882，95% CI = 0.791 - 0.983，P = 0.023），而基于GLIDE联盟的MR分析不支持代谢综合征对牙周炎的因果关系（OR = 0.986，95% CI = 0.920 - 1.057，P = 0.697）。通过多变量MR分析调整潜在混杂因素后，这些结果保持一致。荟萃分析结果不支持代谢综合征对牙周炎的因果关联。敏感性分析表明不存在多效性。在反向分析中，牙周炎与代谢综合征无关联。
在本MR研究范围内，代谢综合征与牙周炎无因果关系。
需要进一步研究以阐明代谢综合征与牙周炎之间的潜在机制。
