ArticleOral health & preventive dentistry2026
Immune-related Plasma Proteins Associated with Recurrent Aphthous Stomatitis Identified by Mendelian Randomization and Clinical Validation.
Article in Oral health & preventive dentistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTo identify immune-related plasma proteins causally associated with susceptibility to recurrent aphthous stomatitis (RAS) through two-sample Mendelian randomization, and to validate their biological and clinical relevance using integrative multi-omics analyses and clinical samples. MATERIALS AND
methodsTwo-sample Mendelian randomization was performed using protein quantitative trait locus (pQTL) data for immune-related plasma proteins from the deCODE genetics database and genome-wide association study (GWAS) summary statistics for RAS to identify proteins with potential causal associations. Candidate proteins were further evaluated by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) network, summary-data-based Mendelian randomization (SMR), and colocalization analyses. Single-cell transcriptomic data from oral mucosa were integrated to characterize the cellular expression patterns of the corresponding genes. Finally, plasma levels of the candidate proteins were measured by enzyme-linked immunosorbent assay (ELISA) in 35 patients with RAS (sampled during both the ulcerative and healing phases) and 35 healthy controls to validate their clinical relevance.
resultsA total of 28 immune-related plasma proteins were identified as having potential causal associations with RAS through two-sample Mendelian randomization. Functional enrichment analysis indicated that these proteins were mainly involved in immune and inflammatory pathways, including natural killer (NK) cell-mediated cytotoxicity, Th1/Th2 cell differentiation, and the IL-17 signaling pathway. SMR and colocalization analyses highlighted IL17A, MMP1, and IL2RA as key candidate genes, with IL17A showing the strongest genetic evidence. Single-cell transcriptomic analysis further revealed distinct cell-type-specific expression patterns of these genes in the oral mucosa. Clinical validation confirmed statistically significant alterations in the plasma levels of IL17A, MMP1, and IL2RA across different stages of RAS.
conclusionsThis integrative study combining genetic analysis, single-cell transcriptomics, and clinical validation identified IL17A, MMP1, and IL2RA as key immune-related molecules associated with RAS. Among them, IL17A showed the strongest genetic evidence and may serve as a promising biomarker and potential therapeutic target for RAS.
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