Shen Jindan, Lou Yimei, Zhang Liping
Department of Stomatology, Yaojiang Township Central Hospital, Zhuji, China.
Front Genet. 2024 May 21;15:1383696. doi: 10.3389/fgene.2024.1383696. eCollection 2024.
Rheumatoid arthritis (RA) frequently presents with oral manifestations, including gingival inflammation, loose teeth, and mouth ulcers; however, the causal connections between these conditions remain unclear. This study aims to explore the genetic correlations and causal relationships between RA and prevalent oral phenotypes.
Using summary data from genome-wide association studies of European populations, a cross-trait linkage disequilibrium score regression was conducted to estimate the genetic correlations between RA and six oral phenotypes. Subsequently, a two-sample Mendelian randomization (MR) approach was employed to assess the causal relationships, corroborated by various sensitivity analyses. Heterogeneity was addressed through the RadialMR method, while potential covariates were corrected using the multivariable MR approach.
A significant negative genetic correlation was detected between RA and denture usage (r = -0.192, = 4.88 × 10). Meanwhile, a heterogenous causal relationship between RA and mouth ulcers was observed (OR = 1.027 [1.005-1.05], = 0.016, = 4.69 × 10), which remained robust across sensitivity analyses. After excluding outlier variants, the results demonstrated robustly consistent (OR = 1.021 [1.008-1.035], = 1.99 × 10, = 0.044). However, upon adjusting for covariates such as smoking, alcohol consumption, body mass index, and obesity, the significance diminished, revealing no evidence to support independent genetic associations.
Genetically predicted RA increases the risk of mouth ulcers, and a negative genetic correlation is identified between RA and denture use. The observed heterogeneity suggests that shared immunological mechanisms and environmental factors may play significant roles. These findings highlight the importance of targeted dental management strategies for RA patients. Further clinical guidelines are required to improve oral health among vulnerable RA patients.
类风湿性关节炎（RA）常伴有口腔表现，包括牙龈炎症、牙齿松动和口腔溃疡；然而，这些情况之间的因果关系仍不清楚。本研究旨在探讨RA与常见口腔表型之间的遗传相关性和因果关系。
利用欧洲人群全基因组关联研究的汇总数据，进行跨性状连锁不平衡评分回归，以估计RA与六种口腔表型之间的遗传相关性。随后，采用两样本孟德尔随机化（MR）方法评估因果关系，并通过各种敏感性分析进行佐证。通过RadialMR方法解决异质性问题，同时使用多变量MR方法校正潜在协变量。
在RA与义齿使用之间检测到显著的负遗传相关性（r = -0.192，P = 4.88 × 10⁻⁶）。同时，观察到RA与口腔溃疡之间存在异质性因果关系（OR = 1.027 [1.005 - 1.05]，P = 0.016，I² = 4.69 × 10⁻²），在敏感性分析中该关系保持稳健。排除异常变异后，结果显示高度一致（OR = 1.021 [1.008 - 1.035]，P = 1.99 × 10⁻³，I² = 0.044）。然而，在调整吸烟、饮酒、体重指数和肥胖等协变量后，显著性降低，未发现支持独立遗传关联的证据。
遗传预测的RA会增加口腔溃疡的风险，并且在RA与义齿使用之间发现了负遗传相关性。观察到的异质性表明，共同的免疫机制和环境因素可能起重要作用。这些发现突出了针对RA患者的针对性牙科管理策略的重要性。需要进一步的临床指南来改善脆弱RA患者的口腔健康。
