Global 5-methylcytosine and 5-hydroxymethylcytosine levels and their clinical associations in metabolic syndrome.

PURPOSE: Metabolic syndrome (MetS) is a complex condition characterized by multiple metabolic abnormalities, in which epigenetic regulation has been increasingly implicated. This study aimed to evaluate global DNA methylation markers, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), in individuals with MetS and examine their associations with clinical and biochemical parameters.

METHODS

A total of 200 patients with MetS and 103 healthy controls were included. Global 5-mC and 5-hmC levels were compared between groups. In the MetS group, correlations between these markers and metabolic, renal, and endocrine parameters were assessed using Spearman correlation analysis.

RESULTS

Global 5-mC levels were significantly higher in MetS patients than in controls (p < 0.001), whereas global 5-hmC levels did not differ between groups. However, 5-hmC levels were negatively correlated with body weight, glycated hemoglobin (HbA1c), triglycerides, creatinine, and thyroid-stimulating hormone (TSH), and positively correlated with high-density lipoprotein cholesterol (HDL-C) and free thyroxine (free T4). In contrast, 5-mC levels showed limited associations with clinical parameters.

CONCLUSION

Global 5-mC levels are elevated in MetS, whereas 5-hmC levels remain unchanged. The broader associations of 5-hmC with clinical and biochemical parameters suggest that hydroxymethylation may provide complementary insight into metabolic heterogeneity in MetS.