Liu Zilin, Huang Xiaoyu, Xie Bingqin, Huang Yu, He Baochang, Luo Lan, Liu Huanhuan, Chen Fa
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.
Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Oral Diseases, School of Stomatology, Fujian Medical University, Fuzhou, China.
Int Dent J. 2025 Apr;75(2):683-691. doi: 10.1016/j.identj.2024.10.025. Epub 2024 Dec 18.
While observational studies have demonstrated a potential link between inflammatory cytokines and oral diseases, the question of causality is warranting further investigation. This study aimed to comprehensively assess the potential causal role of 41 inflammatory cytokines in common oral diseases.
A two-sample Mendelian randomization (MR) study was conducted using the summary statistics from the largest publicly available genome-wide association study (GWAS) for 41 inflammatory cytokines and common oral diseases (indicated by the index of decayed and filled tooth surfaces divided by number of tooth surfaces (DFSS), index of decayed, missing and filled tooth surfaces (DMFS), number of natural teeth, and periodontitis). Inverse variance weighted regression (IVW) was used as the primary method to estimate odds ratios (OR) and 95% confidence interval (CI) for assessing the causal effect. Sensitivity analyses with other four analytical approaches were performed to test the validity of our findings.
Increased levels of hepatocyte growth factor (HGF) and stem cell growth factor beta (SCGF-β) were significantly associated with the risk of DFSS, with the ORs of 1.058 (95% CI: 1.004-1.115, P = .033) and 1.035 (95% CI:1.002-1.069, P = .038), respectively. Interleukin-1 receptor antagonist (IL-1RA) exhibited a negative association with DMFS (OR = 0.934, 95% CI: 0.886-0.985, P = .012). Furthermore, interleukin-9 (IL-9) was associated with in increased risk of periodontitis (OR = 1.148, 95% CI:1.031-1.277, P = .011). Additionally, no significant association was found between inflammatory cytokines and the number of natural teeth. Sensitivity analyses yielded generally consistent results.
This MR study provides evidence supporting potential causal associations of four inflammatory cytokines (HGF, SCGF-β, IL-1RA, IL-9) with the risk of common oral diseases, which may contribute to the development of more targeted prevention strategies for these diseases.
虽然观察性研究已证明炎症细胞因子与口腔疾病之间存在潜在联系，但因果关系问题仍需进一步研究。本研究旨在全面评估41种炎症细胞因子在常见口腔疾病中的潜在因果作用。
采用来自最大的公开可用全基因组关联研究（GWAS）的汇总统计数据，进行两样本孟德尔随机化（MR）研究，该研究涉及41种炎症细胞因子和常见口腔疾病（用龋补牙面数除以牙面总数（DFSS）、龋失补牙面指数（DMFS）、天然牙数量和牙周炎指数表示）。逆方差加权回归（IVW）用作估计比值比（OR）和95%置信区间（CI）以评估因果效应的主要方法。采用其他四种分析方法进行敏感性分析，以检验我们研究结果的有效性。
肝细胞生长因子（HGF）和干细胞生长因子β（SCGF-β）水平升高与DFSS风险显著相关，其OR分别为1.058（95%CI：1.004 - 1.115，P = 0.033）和1.035（95%CI：1.002 - 1.069，P = 0.038）。白细胞介素-1受体拮抗剂（IL-1RA）与DMFS呈负相关（OR = 0.934，95%CI：0.886 - 0.985，P = 0.012）。此外，白细胞介素-9（IL-9）与牙周炎风险增加相关（OR = 1.148，95%CI：1.031 - 1.277，P = 0.011）。此外，未发现炎症细胞因子与天然牙数量之间存在显著关联。敏感性分析得出的结果总体一致。
这项MR研究提供了证据，支持四种炎症细胞因子（HGF、SCGF-β、IL-1RA、IL-9）与常见口腔疾病风险之间存在潜在因果关联，这可能有助于制定针对这些疾病的更具针对性的预防策略。
