A novel diagnostic model for HIV-HTN comorbidity: genomic discovery, clinical validation, and mechanistic elucidation

Hypertension (HTN) is a frequent comorbidity in people living with Human Immunodeficiency Virus (HIV), yet the shared molecular determinants remain poorly defined. This study aimed to identify diagnostic biomarkers and regulatory networks underlying HIV-HTN comorbidity.

Transcriptomic datasets from HIV (GSE140713) and HTN (GSE236442) cohorts were analyzed to screen differentially expressed genes. Functional enrichment, GSEA, and PPI analyses were performed to uncover shared pathways and hub genes. Immune cell infiltration was evaluated using CIBERSORT. Transcriptional and post-transcriptional regulatory networks were constructed through NetworkAnalyst, miRNet, and starBase. Key genes were validated in peripheral blood samples from healthy individuals, HIV patients, and HIV-HTN patients using qRT-PCR.

A total of 109 overlapping genes were identified, converging on cytokine-cytokine receptor interaction, IL-17, and NF-κB pathways. Six hub genes (FOS, PTGS2, TRMT2A, E2F1, FASN, STAB1) were shared across both diseases. Immune deconvolution showed prominent involvement of DC, monocytes, macrophages, NK/NKT cells, and T-cell subsets. qRT-PCR confirmed consistent upregulation of TRMT2A, E2F1, FASN, and STAB1, and downregulation of FOS and PTGS2. A putative ceRNA network was constructed, highlighting several candidate regulatory miRNAs and lncRNAs.

This integrative analysis suggests potential molecular signatures and immune-related regulatory axes that may contribute to HIV-HTN comorbidity, providing hypothesis-generating leads for biomarker discovery and mechanistic follow-up studies.