Int J Stomatol

Int J Stomatol ›› 2026, Vol. 53 ›› Issue (2): 205-215.doi: 10.7518/gjkq.2026003

• Original Articles • Previous Articles    

Exploring the impact of mitochondrial dysfunction on the pathogenesis of oral lichen planus using Mendelian randomization

Manman Yao(),Yueting Lu(),Jingjing Wu,Tiejun Liu,Yongle Qiu,Hongyue Shang,Bo Dong   

  1. Dept. of Stomatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Received:2024-11-05 Revised:2024-12-30 Online:2026-03-01 Published:2026-02-13
  • Contact: Yueting Lu E-mail:49103567@hebmu.edu.cn;48901999@hebmu.edu.cn
  • Supported by:
    Central Government Guides Local Funds Supported by S&T Program of Hebei(246Z7762G);Research Plan of Hebei Provincial Administration of Traditional Chinese Medicine(2026349);Medical Science Research Project of Hebei Province(20260512)

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Abstract:

Objective　This study aimed to investigate 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 mitochondrial-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 identified 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-recycling 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 relationship 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 translational functions, including MCD, MRPL34, and RRF, may contribute to increased disease risk. The bidirectional association 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.

Key words: oral lichen planus, Mendelian randomization analysis, mitochondria

CLC Number: 

  • R781.5

TrendMD: 

Fig 1

Heatmap showing the correlation between mitochondrial traits and OLP"

Tab 1

Mitochondria-related genome-wide association study (GWAS) data associated with OLP"

编号（GWAS ID）年份线粒体因子样本量SNP数量
prot-a-19532018MPMSR3 30110 534 735
prot-a-19072018MCD3 30110 534 735
prot-a-12202018Grx23 30110 534 735
prot-a-19432018MRPL343 30110 534 735
prot-a-19452018RRF3 30110 534 735

Fig 2

Forest plot of the causal relationship between mitochondria and OLP (integrated five algorithms)"

Fig 3

Forest plot of the causal relationship between mitochondria and OLP (IVW algorithm)"

Tab 2

Results of heterogeneity and pleiotropic tests"

编号

线粒体

因子

结局异质性检验水平多效性检验
MR EggerIVW
Egger截距SEP值
QQ_dfQ_PQQ_dfQ_P
prot-a-1220Grx2OLP10.1100.43412.4110.333-0.0910.060.159
prot-a-1953MPMSROLP6.5170.4816.5280.5890.0100.1010.926
prot-a-1907MCPOLP10.770.15110.980.205-0.0310.0840.723
prot-a-1943MRPL34OLP0.05620.9723.35830.3400.6480.3570.211
prot-a-1945RRFOLP6.8290.6567.55100.6720.0450.0530.412

Fig 4

Forest plot of five key mitochondrial traits causally associated with OLP"

Fig 5

Scatter plot of five key mitochondrial traits causally associated with OLP"

Fig 6

Leave-one-out forest plot of five key mitochondrial traits causally associated with OLP"

Fig 7

Funnel plot of five key mitochondrial traits causally associated with OLP"

Fig 8

Forest plot of reverse validation causal relationship between MCD and OLP"

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