Objective  To explore the potential molecular mechanisms by which bisphenol A (BPA) regulates atopic dermatitis (AD).

Methods  The AD-related targets were screened from the OMIM and GeneCards databases, and BPA targets were screened from the SwissTargetPrediction and ChEMBL databases. Venn diagrams were used to obtain common gene targets of BPA and AD. Gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, as well as cluster analyses were conducted on the common targets. Core targets were identified by combining LASSO regression and random forest with differential genes from the GSE121212 dataset. CIBERSORTx was applied to analyze immune cell infiltration, and the pROC and rms packages were employed to construct an AD risk prediction model to evaluate predictive performance. AutoDockTools 1.5.7 and AutoDock Vina 1.2.0 were used for molecular docking between core targets and BPA.

Results  The study identified 1,053 AD-related targets and 135 BPA targets, resulting in 57 intersecting target genes that were significantly enriched in immune-related pathways. Histamine receptor H1 (HRH1), lymphocyte-specific protein tyrosine kinase (LCK), and platelet-activating factor receptor (PTAFR) were identified as core targets, all of which were significantly upregulated in AD lesion tissues. The binding affinities of BPA with core targets were all < -5.0 kcal/mol; core targets were positively correlated with CD4+ memory T cells and dendritic cells, and negatively correlated with M0 macrophages. The area under the curve (AUC) of the gene target combination model was 0.915 [95%CI (0.856, 0.974)].

Conclusion  HRH1, LCK, and PTAFR are core targets of BPA in regulating AD, and BPA may trigger an imbalance in the immune microenvironment of AD by regulating these core targets.

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