牙周炎和血浆炎症因子与良性前列腺增生之间的关联:一项中介孟德尔随机化研究  

The association between periodontitis,plasma inflammatory factors,and benign prostatic hyperplasia:a mediation Mendelian randomization study

作　　者：贾海昌 樊九铭 方程 曾宪涛[1,2] JIA Haichang;FAN Jiuming;FANG Cheng;ZENG Xiantao(Department of Urology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Center for Evidence-Based and Translational Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Department of Urology,Huaihe Hospital of Henan University,Kaifeng 475400,Henan Province,China)

机构地区：[1]武汉大学中南医院泌尿外科,武汉430071 [2]武汉大学中南医院循证与转化医学中心,武汉430071 [3]河南大学淮河医院泌尿外科,河南开封475400

出　　处：《医学新知》2025年第3期312-318,I0010,I0011,共9页New Medicine

基　　金：国家自然科学基金青年科学基金项目(82100817)。

摘　　要：目的利用双样本孟德尔随机化(Mendelian randomization,MR)研究方法探究牙周炎(periodontitis,PD)、慢性牙周炎(chronic periodontitis,CP)、复杂性慢性牙周炎(complicated chronic periodontitis,CCP)与良性前列腺增生(benign prostatic hyperplasia,BPH)的因果关系以及血浆炎症因子的中介作用。方法使用FinnGen与GWAS项目的BPH、PD、CP、CCP,以及循环炎症因子水平的遗传数据进行双样本MR分析。使用逆方差加权(inverse-variance weighting,IVW)、MR Egger、加权中位数、简单众数法和加权众数法进行分析。使用IVW分析血浆炎症因子在CCP与BPH之间的中介效应。结果IVW显示PD、CP与BPH不存在显著的因果关系,CCP增加BPH的发生风险[OR=1.14,95%CI(1.04,1.25),P_(FDR)=0.028]。白血病抑制因子[OR=1.14,95%CI(1.02,1.28),P_(FDR)=0.024]和C-C基序趋化因子28[OR=1.11,95%CI(1.00,1.23),P_(FDR)=0.047]可以促进BPH;活化诱导的受体核因子κB配体[OR=0.89,95%CI(0.81,0.99),P_(FDR)=0.024]、Fms样酪氨酸激酶3配体[OR=0.88,95%CI(0.79,0.98),P_(FDR)=0.022]、抑瘤素M[OR=0.84,95%CI(0.72,0.98),P_(FDR)=0.022]、C-X-C基序趋化因子9[OR=0.83,95%CI(0.74,0.93),P_(FDR)=0.001]和半胱氨酸天冬氨酸蛋白酶8[OR=0.82,95%CI(0.69,0.96),P_(FDR)=0.015]的血浆水平与BPH风险具有显著负向关联。但这些炎症因子在CCP与BPH之间并不存在显著的中介效应。结论CCP会增加BPH的发生风险,部分炎症因子也会增加BPH发生风险,但这些炎症因子未介导CCP对BPH的作用,未来仍需进一步研究CCP增加BPH发生风险的相关机制。Objective To investigate the potential causal relationships between periodontitis(PD),chronic periodontitis(CP),complicated chronic periodontitis(CCP),and benign prostatic hyperplasia(BPH),as well as the mediating effect of plasma inflammatory factors,using a two-sample Mendelian randomization(MR)approach.Methods Genetic data on BPH,PD,CP,CCP,and circulating inflammatory factors levels were obtained from the FinnGen and GWAS projects for two-sample MR analysis.The inverse-variance weighting(IVW)method,MR-Egger,weighted median,simple mode,and weighted mode methods were employed for analyses.The mediating effect of plasma inflammatory factors on the association between CCP and BPH was assessed using IVW.Results The IVW analysis indicated no significant causal relationship between PD,CP,and BPH.However,CCP was associated with an increased risk of BPH[OR=1.14,95%CI(1.04,1.25),P_(FDR)=0.028].Among inflammatory factors,leukemia inhibitory factor[OR=1.14,95%CI(1.02,1.28),P_(FDR)=0.024]and C-C motif chemokine 28[OR=1.11,95%CI(1.00,1.23),P_(FDR)=0.047]were found to promote BPH.Conversely,plasma levels of TNF-related activation-induced cytokine[OR=0.89,95%CI(0.81,0.99),P_(FDR)=0.024],Fms-like tyrosine kinase 3 ligand[OR=0.88,95%CI(0.79,0.98),P_(FDR)=0.022],Oncostatin M[OR=0.84,95%CI(0.72,0.98),P_(FDR)=0.022],C-X-C motif chemokine 9[OR=0.83,95%CI(0.74,0.93),P_(FDR)=0.001],and caspase-8[OR=0.82,95%CI(0.69,0.96),P_(FDR)=0.015]were significantly negatively associated with BPH risk.However,no significant mediating effect of these inflammatory factors was observed in the association between CCP and BPH.Conclusion CCP increases the risk of BPH,and certain inflammatory factors also contribute to BPH risk.However,these factors do not mediate the effect of CCP on BPH.Further studies are needed to elucidate the mechanisms underlying the association between CCP and BPH risk.

关 键 词：牙周炎 良性前列腺增生 炎症因子 孟德尔随机化 中介分析 

分 类 号：R697.3[医药卫生—泌尿科学] R781.42[医药卫生—外科学]