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

JIA Haichang; FAN Jiuming; FANG Cheng; ZENG Xiantao

doi:10.12173/j.issn.1004-5511.202412135

Abstract：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),PFDR=0.028].Among inflammatory factors,leukemia inhibitory factor[OR=1.14,95%CI(1.02,1.28),PFDR=0.024]and C-C motif chemokine 28[OR=1.11,95%CI(1.00,1.23),PFDR=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),PFDR=0.024],Fms-like tyrosine kinase 3 ligand[OR=0.88,95%CI(0.79,0.98),PFDR=0.022],Oncostatin M[OR=0.84,95%CI(0.72,0.98),PFDR=0.022],C-X-C motif chemokine 9[OR=0.83,95%CI(0.74,0.93),PFDR=0.001],and caspase-8[OR=0.82,95%CI(0.69,0.96),PFDR=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.