慢性牙周炎与帕金森病之间潜在相关性的初探

Potential correlation between chronic periodontitis and Parkinson’s disease

目的探讨慢性牙周炎(CP)和帕金森病(PD)之间潜在的核心基因、相关通路和转录因子。方法从基因表达综合(GEO)数据库下载CP(GSE16134、GSE23586和GSE10334)和PD(GSE20141和GSE49036)的基因表达谱进行差异表达分析、功能聚类分析,并构建蛋白质相互作用(PPI)网络,通过4种拓扑分析算法和模块划分筛选出核心基因,进行转录因子的预测及功能聚类分析。通过CP和PD的外部数据集对核心基因进行验证,并通过双本孟德尔随机化(MR)进一步评估二者的因果关系。结果合并数据后,CP数据集共筛选出1211个差异表达基因(DEG),其中551个上调,660个下调,PD数据集共筛选出2407个DEG,其中1438个上调,969个下调;PPI网络包括145个节点和126条边,最终筛选出4个核心基因,分别为FCGR3B、PRF1、IL18和CD33;预测的转录因子包括HSF1、HSF2和HSF4;相关通路主要为自然杀伤细胞(NK)介导的细胞毒性作用;MR结果表明,CP与PD的发病风险可能呈正向因果关系。结论本研究探索了CP和PD的潜在共同发病机制及可能的因果关系,为进一步的机制研究提供新思路,预测的转录因子为可能的治疗靶点提供新见解。

Objective This study aims to investigate possible hub genes,associated pathways,and transcription factors between chronic periodontitis(CP)and Parkinson’s disease(PD).Methods Gene expression profiles of CP(GSE16134,GSE23586,and GSE10334)and PD(GSE20141 and GSE49036)were downloaded from the gene expression omnibus(GEO)database for differential expression analysis and functional clustering analysis.The protein-protein interaction(PPI)network was constructed,and hub genes were screened by four topological analysis algorithms and modular segmentation.Functional clustering analysis was performed.The hub genes were validated by external datasets of CP and PD,and causal relation was further assessed by Mendelian randomization(MR).Results After merging the data,1211 differentially expressed genes(DEGs)were screened in the CP datasets;of which,551 were upregulated and 660 were downregulated.A total of 2407 DEGs were screened in the PD dataset,of which,1438 were upregulated and 969 were downregulated.The PPI network included 145 nodes and 126 edges.Four hub genes(FCGR3B,PRF1,IL18,and CD33)and three transcription factors(HSF1,HSF2,and HSF4)were finally screened.The relevant pathway was predominantly natural killer(NK)cell-mediated toxic effects.The MR results suggest a possible positive causal relationship between CP and the risk of developing PD.Conclusion This study indicated the probably shared pathophysiology and possible causal relationship between CP and PD and may offer novel concepts and therapeutic targets for future mechanistic investigations.