采用孟德尔随机化法研究线粒体功能障碍对口腔扁平苔藓发病机制的影响OA

Objective This study aimed to investi-gate the potential causal relationship between specific mitochondrial functions and oral lichen planus (OLP)via Mendelian randomization (MR) analysis. To explore the effect of mitochondrial dysfunction on OLP,provi-ding new insights into its pathogenesis and identifying potential therapeutic targets. Methods Genetic variants related to mitochondrial function were obtained from the integrative epidemiology unit open GWAS project (IEU) database,and OLP summary-level data (587 cases and 411 594 controls) were retrieved from the FINNGEN database. A total of 69 mi-tochondrial-related genetic variants were selected for analysis. MR analysis was performed using R software (version 4.3.2),applying the inverse variance weighted (IVW) method,MR Egger regression,and the weighted median approach to estimate the causal effects of mitochondrial variants on OLP. Instrumental variables were selected with a significance threshold of P<5e-5. To eliminate linkage disequilibrium,single-nucleotide polymorphisms (SNPs) within 1 000 kb and with r²>0.001 were excluded. Heterogeneity and horizontal pleiotropy were also assessed. Results MR analysis identi-fied significant associations between specific mitochondrial functions and OLP. Odds ratios (OR) less than 1 suggested a protective effect on OLP. Glutaredoxin-2 (Grx2) (IVW,OR:0.768,P=0.036) and mitochondrial peptide methionine sulfo-xide reductase (MPMSR) (IVW,OR:0.680,P=0.044) had ORs less than 1. Conversely,malonyl-CoA decarboxylase(MCD) (IVW,OR:1.591,P=0.022),39S ribosomal protein L34 (MRPL34) (IVW,OR:1.826,P=0.034),and ribosome-re-cycling factor (RRF) (IVW,OR:1.498,P=0.004 9) exhibited OR greater than 1,indicating that they were risk factors for OLP. Further reverse validation showed that MCD was significantly associated with OLP (IVW,OR:1.134,P=0.045),suggesting that OLP was a risk factor for this mitochondrial function. Conclusion This MR study identified a causal re-lationship between specific mitochondrial functions and OLP. Mitochondrial proteins involved in redox homeostasis,such as Grx2 and MPMSR,appear to have a protective effect,whereas dysregulation of mitochondrial metabolic and transla-tional functions,including MCD,MRPL34,and RRF,may contribute to increased disease risk. The bidirectional associa-tion between MCD and OLP further highlights the complexity of mitochondrial involvement in OLP pathogenesis. These findings provide novel insights into potential causal pathways and therapeutic targets for OLP.