国际口腔医学杂志2026，Vol.53Issue(2)：205-215,11.DOI:10.7518/gjkq.2026003
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
Exploring the impact of mitochondrial dysfunction on the pathogenesis of oral lichen planus using Mendelian ran-domization
摘要
Abstract
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.关键词
口腔扁平苔藓/孟德尔随机化分析/线粒体Key words
oral lichen planus/Mendelian randomization analysis/mitochondria分类
医药卫生引用本文复制引用
姚曼曼,路月亭,吴景景,刘铁军,仇永乐,尚宏悦,董博..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[J].国际口腔医学杂志,2026,53(2):205-215,11.基金项目
Central Government Guides Local Funds Supported by S&T Program of Hebei(246Z7762G) （246Z7762G）
Research Plan of Hebei Provincial Administration of Traditional Chinese Medicine(2026349) （2026349）
Medical Science Research Project of Hebei Province(20260512) 中央引导地方科技发展资金(246Z7762G) （20260512）
河北省中医药管理局科学研究课题计划(2026349) （2026349）
河北省医学科学研究课题计划(20260512) （20260512）
