评估 Epstein-Barr 病毒暴露及其基因特征对牙周炎的终生影响。

IF 4.2 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Xinjian Ye, Jian Yuan, Yijing Bai, Yitong Chen, He Jiang, Yue Cao, Qifei Ge, Zhiyong Wang, Weiyi Pan, Shan Wang, Qianming Chen
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引用次数: 0

摘要

背景:牙周炎产生于环境变量和遗传易感性的多方面相互作用,其中微生物感染起着不可或缺的作用。长期以来,人们一直认为EB病毒(Epstein-Barr virus,EBV)暴露与牙周炎活动有关;然而,它们之间的因果关系和遗传联系仍然未知:我们的研究采用孟德尔随机化(Mendelian randomization,MR)方法,包括单变量、多变量、贝叶斯模型平均和反向 MR,在生命过程的背景下研究 EBV 暴露与牙周炎之间的因果关系。此外,还利用连锁不平衡得分回归和共定位分析来评估跨性状遗传相关性,然后利用全转录组关联分析和富集分析来鉴别遗传表型生物特征:结果:EB病毒抗体水平升高,尤其是早期抗原扩散(作为早期感染或再激活的指标),与牙周炎风险增加有关(比值比[OR]:1.27 [1.09-1.47],p = 6.05 × 10-3),并显示出显著的遗传相关性(p = 4.11 × 10-3)。这种发病机制可能涉及位于 17p13.1 的高置信度致病基因 RNASEK。遗传预测的生命早期抗 EBV 免疫球蛋白 G (IgG) 水平与牙周炎风险降低相关(OR:0.89 [0.82-0.97],p = 1.76 × 10-3):本研究强调了EBV暴露及其遗传特征对牙周炎的影响,为EBV相关牙周炎的潜在发病机制和管理策略提供了新的视角。这些发现强调了不同的临床和公共卫生影响,包括抗病毒疗法、病毒疫苗接种策略和个性化牙周炎管理的定制干预措施。我们还需要进一步的研究来验证和扩展我们的发现。白话摘要:牙周炎是一种慢性炎症性疾病,由微生物病原体和宿主免疫系统之间的相互作用驱动。虽然细菌一直是研究的重点,但最近的研究强调了病毒-细菌相互作用的重要性,尤其是 Epstein-Barr 病毒(EBV)--一种感染全球 90% 以上人口的疱疹病毒--在牙周炎发病中的作用。然而,潜在的成因和遗传机制仍不清楚。我们的研究采用了全基因组多组学方法来研究 EBV 暴露与牙周炎之间的联系。我们发现,近期的 EBV 感染或再激活会增加牙周炎的风险,而早年的暴露则可能会降低牙周炎的风险,因为早年的暴露可能会增强免疫抵抗力。基本基因被确定为潜在的介导因素,包括 CRTC3-AS1、HLA-DQA1 和 RNASEK。这些研究结果为了解 EBV 与牙周炎的关系提供了新的视角。例如,病毒检测和控制可使对标准细菌疗法无反应的患者受益,通过接种疫苗及早接触病毒可降低牙周炎的风险。要阐明这些基本机制以及病毒与细菌相互作用的贡献,还需要进一步的临床研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Appraising the life-course impact of Epstein-Barr virus exposure and its genetic signature on periodontitis.

Background: Periodontitis arises from a multifaceted interplay of environmental variables and genetic susceptibility, where microbial infection plays an indispensable part. Epstein-Barr virus (EBV) exposure has long been considered associated with periodontitis activity; however, the causal relationship and genetic connection between them remain unknown.

Methods: Within a life-course context, our study employed comprehensive Mendelian randomization (MR) methods, including univariable, multivariable, Bayesian model averaging, and reverse MR, to investigate the causal association between EBV exposure and periodontitis. Additionally, linkage disequilibrium score regression and colocalization analysis were utilized to assess the cross-trait genetic correlations, followed by transcriptome-wide association and enrichment analysis to discern the genetic-phenotypic biological profiles.

Results: Heightened levels of EBV antibodies, particularly early antigen diffuses (which serve as indicators of early infection or reactivation), are associated with an increased risk of periodontitis (odds ratio [OR]: 1.27 [1.09-1.47], p = 6.05 × 10-3) and demonstrate a significant genetic correlation (p = 4.11 × 10-3). This pathogenesis may involve the high-confidence causal gene RNASEK located in 17p13.1. Genetically predicted early-life anti-EBV immunoglobulin G (IgG) levels are correlated to a reduced periodontitis risk (OR: 0.89 [0.82-0.97], p = 1.76 × 10-3).

Conclusions: The present study highlights the impact of life-course EBV exposure and its genetic hallmark on periodontitis, providing novel perspectives into the underlying pathogenesis and management strategies for EBV-related periodontitis. These findings underscore diverse clinical and public health implications, encompassing antiviral therapies, viral vaccination strategies, and tailored interventions for individualized periodontitis management. Further research is required to validate and expand upon our findings.

Plain language summary: Periodontitis is a chronic inflammatory disease driven by interactions between microbial pathogens and the host immune system. While bacteria have traditionally been the focus of research, recent studies highlight the significance of virus-bacteria interactions, particularly the role of Epstein-Barr virus (EBV)-a herpesvirus infecting over 90% of the global population-in the development of periodontitis. However, the underlying causal and genetic mechanisms remain unclear. Our study employed genome-wide multi-omics approaches to investigate the link between EBV exposure and periodontitis. We found that recent EBV infection or reactivation increases the risk of periodontitis, whereas early-life exposure, possibly enabling immune resistance, may reduce it. Essential genes were identified as potential mediators, including CRTC3-AS1, HLA-DQA1, and RNASEK. These findings provide novel insights into the EBV-periodontitis connection. For example, viral testing and control could benefit patients unresponsive to standard bacterial treatments, and early viral exposure via vaccination might reduce the risk of periodontitis. Further clinical studies are required to elucidate these underlying mechanisms and the contribution of virus-bacteria interactions.

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来源期刊
Journal of periodontology
Journal of periodontology 医学-牙科与口腔外科
CiteScore
9.10
自引率
7.00%
发文量
290
审稿时长
3-8 weeks
期刊介绍: The Journal of Periodontology publishes articles relevant to the science and practice of periodontics and related areas.
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