|
Metabolic syndrome (MetS) is a multifactorial disorder caused by the interplay of genetic, epigenetic, and environmental factors. Although aberrant DNA methylation changes are significantly associated with the pathogenesis of many diseases, little is known about the molecular mechanisms underlying interactions between DNA methylation and gene expression in MetS. The aim of this study was to identify biomarkers and molecular mechanisms regulated by DNA methylation in MetS on a genome-wide scale. We profiled genome-wide DNA methylation profiling using the Infinium MethylationEPIC BeadChIP (Illumina) and characterized the whole transcriptome by RNA sequencing in our study population comprised of subjects with MetS (n=11) and controls (n=9). In total, 13,707 significantly differentially methylated probes (DMPs) were identified in blood samples of subjects with MetS, most in the promoter and coding regions. Among them, 47 DMPs were significantly correlated with the expression of 36 corresponding genes, which were enriched in ‘insulin resistance’, ‘insulin signaling pathway’, and the ‘apelin signaling pathway’. Among these MetS-associated genes, validation of the most discriminating gene via ROC curve analysis, GFPT2, showed significant hypermethylation/downregulated expression in subjects with MetS compared to that in normal controls via bisulfite amplicon sequencing and quantitative real-time PCR. Our findings demonstrated altered DNA methylation in subjects with MetS, suggesting that GFPT2 hypermethylation might be a promising epigenetic biomarker and emphasizing the role of aberrant GFPT2 expression in MetS pathogenesis. Further, the genes identified in the current study could play important roles in regulating MetS mechanisms, especially insulin-related pathways, which might provide markers for MetS diagnosis. |
