慢性牙周炎与帕金森病之间潜在相关性的初探

doi:10.7518/hxkq.2024.2024010

摘要/Abstract

摘要：

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1 211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2 407个DEG，其中1 438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。

关键词: 慢性牙周炎, 帕金森病, 核心基因, 转录因子, 孟德尔随机化

Abstract:

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, 1 211 differentially expressed genes (DEGs) were screened in the CP datasets; of which, 551 were upregulated and 660 were downregulated. A total of 2 407 DEGs were screened in the PD dataset, of which, 1 438 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.

Key words: chronic periodontitis, Parkinson’s disease, hub gene, transcription factor, Mendelian randomization

中图分类号:

R781.4

杨荣霞, 宗颖睿, 张晨. 慢性牙周炎与帕金森病之间潜在相关性的初探[J]. 华西口腔医学杂志, 2024, 42(4): 521-530.

Yang Rongxia, Zong Yingrui, Zhang Chen. Potential correlation between chronic periodontitis and Parkinson’s disease[J]. West China Journal of Stomatology, 2024, 42(4): 521-530.

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疾病	数据集	取样部位	芯片平台	病例样本数/个	对照样本数/个	总样本数/个	上调DEG数/个	下调DEG数/个	总DEG数/个	\|log2FC\|	P值
CP	GSE16134	牙龈组织	GPL570	241	69	310	551	660	1 211	>1	<0.05
	GSE23586	牙龈组织	GPL570	3	3	6
	GSE10334	牙龈组织	GPL570	183	64	247
PD	GSE20141	脑黑质组织	GPL570	10	8	18	1 438	969	2 407	>1	<0.05
PD	GSE49036	脑黑质组织	GPL570	20	8	28	1 438	969	2 407	>1	<0.05

疾病	数据集	取样部位	芯片平台	病例样本数/个	对照样本数/个	总样本数/个
CP	GSE173078	牙龈组织	GPL10301	12	12	24
CP	GSE79705	牙龈组织	GPL18734	4	4	8
PD	GSE20163	脑黑质组织	GPL6480	9	8	17
PD	GSE7621	脑黑质组织	GPL570	16	9	25

疾病	编码号	病例	对照	SNP	种族
CP	finn-b-K11_GINGIVITIS_PERIODONTAL	4 120	195 395	16 380 400	欧洲
PD	finn-b-PD-DEMENTIA_EXMORE	267	111 621	16 379 396	欧洲

基因名称	全称	MCC	MNC	Degree	EPC
CTLA4	细胞毒性T淋巴细胞蛋白4	109	9	20	28.069
TLR2	Toll样受体2	105	10	22	28.139
FCGR3B	Fcγ受体Ⅲb	97	11	24	28.136
PRF1	穿孔素1	79	7	16	27.98
IL18	白细胞介素18	56	7	14	27.896
CD33	骨髓细胞表面抗原CD33	50	6	12	27.679
IL12RB1	白细胞介素12受体亚基β1	30	5	14	27.2
PECAM1	血小板和内皮细胞黏附分子1	28	5	16	27.321
CD300A	CD300抗原样家族成员A	17	6	14	27.34
LILRB1	白细胞免疫球蛋白样受体B1	16	5	14	27.683

类别	条目	功能	P值	校正P值	基因名	数目
生物学过程	GO：0002443	白细胞介导的免疫	4.20×10^-6	2×10^-3	FCGR3B/PRF1/IL18/CD33	4
	GO：0045321	白细胞激活	1.91×10^-5	3×10^-3	FCGR3B/PRF1/IL18/CD33	4
	GO：0002252	免疫效应过程	2×10^-5	3×10^-3	FCGR3B/PRF1/IL18/CD33	4
细胞定位	GO：0044194	溶细胞颗粒	8×10^-4	2×10^-2	PRF1	1
	GO：0030667	分泌颗粒膜	1.4×10^-3	2×10^-2	FCGR3B/CD33	2
	GO：0044433	细胞质囊泡部分	1.7×10^-3	2×10^-2	FCGR3B/PRF1/CD33	3
分子功能	GO：0019864	IgG结合	1×10^-3	4×10^-2	FCGR3B	1
	GO：0033691	唾液酸结合	2×10^-3	4×10^-2	CD33	1
	GO：0022829	宽孔道活性	3×10^-3	4×10^-2	PRF1	1
KEGG	hsa04650	自然杀伤细胞介导细胞毒性	1.5×10^-3	4×10^-2	FCGR3B/PRF1	2
	hsa05152	结核病	3×10^-3	4×10^-2	FCGR3B/IL18	2
	hsa05143	非洲锥虫病	1.8×10^-2	7×10^-2	IL18	1