Vitamin E-Related Molecular Signatures in Adolescent Idiopathic Scoliosis: A Hypothesis-Generating Multi-Omics Analysis.

Adolescent idiopathic scoliosis (AIS) involves systemic bone-metabolic dysregulation and paraspinal microenvironment remodeling, but whether nutrition-related micronutrient-associated molecular programs overlap with these alterations remains unclear. Vitamin E (VE), comprising lipid-soluble tocopherols and tocotrienols, is linked to membrane protection, lipid peroxidation control, inflammatory mediator regulation, and endothelial responses. This study examined whether VE-related molecular signatures converge on AIS-associated redox, lipid-inflammatory, vascular, and multicellular remodeling programs. Peripheral blood miRNA data (GSE235203) and bone marrow transcriptomic data (GSE110359) were integrated using HERB-based compound mapping, VE-AIS shared-target enrichment, feature prioritization, intradisease GSEA, single-cell localization, CellChat analysis, and NHANES contextualization. HERB mapping generated a VE/tocopherol-related prioritization signal, not direct evidence of VE involvement in AIS. Forty-two shared VE-AIS targets were enriched mainly in oxidative stress, glutathione/peroxidase activity, and glutathione metabolism, with additional lipid-inflammatory and vascular signals. Five prioritized genes (SOD1, GCLC, PTGS1, PTGS2, and KDR) defined redox-buffering, lipid-inflammatory, and vascular-response axes. Single-cell and CellChat analyses localized these signatures mainly to endothelial, dendritic/APC-like, MSC-like, and stromal/osteogenic populations, suggesting a predicted concave-side enrichment of inflammatory-endothelial-stromal communication. Structural analyses supported the computational plausibility of α-tocopherol compatibility with selected proteins, particularly PTGS2. No AIS cohort with measured VE exposure or status was analyzed. NHANES provided external clinical nutrition context rather than AIS-specific validation. Overall, VE-related signatures overlapped with redox, lipid-inflammatory, vascular-response, and multicellular remodeling programs in AIS. These findings generate testable molecular hypotheses but do not show that VE intake, tocopherol status, or supplementation modifies AIS risk, severity, or progression.