Transcriptomic Alterations in Peripheral Blood of Patients with Metabolic Syndrome

Metabolic syndrome (MetS) is a complex cardiometabolic disorder characterized by interconnected abnormalities in glucose and lipid metabolism, adiposity, and vascular regulation. Transcriptomic profiling may provide insight into molecular alterations associated with MetS. This study aimed to identify peripheral blood gene expression changes in MetS using RNA sequencing and to evaluate selected candidate genes by RT-qPCR in an independent cohort. RNA sequencing was performed in 15 patients with MetS and 10 healthy controls; after exclusion of three MetS samples based on PCA, differential expression analysis included 12 patients with MetS and 10 controls. Six candidate genes (FKBP1B, PLIN2, ARVCF, NAA40, ALOX15B, and MUSTN1) were subsequently evaluated by RT-qPCR in an independent cohort of 146 patients with MetS and 116 controls. Relative expression changes were calculated using the 2^−ΔΔCt method, and multiple testing was controlled using the Benjamini–Hochberg false discovery rate (FDR) procedure. Among 19,668 protein-coding genes, 730 showed nominal differential expression (p < 0.05), whereas only FKBP1B and EVA1C remained significant after FDR correction. In the RT-qPCR cohort, FKBP1B, ARVCF, and NAA40 showed significantly higher expression in MetS, corresponding to 6.33-, 1.87-, and 2.34-fold increases, respectively; all remained significant after FDR correction. No significant differences were observed for PLIN2, ALOX15B, or MUSTN1. Exploratory analyses identified no robust associations between candidate-gene expression and metabolic or cardiovascular clinical parameters after multiple-testing correction. FKBP1B remained significant after transcriptome-wide FDR correction and showed concordant upregulation in the independent RT-qPCR cohort, while the nominal RNA-seq candidates ARVCF and NAA40 also showed significantly increased expression by RT-qPCR. These findings identify transcriptional alterations associated with MetS and warrant further validation in independent cohorts and functional studies.