Gfpt2 Promoter Methylation in Metabolic Syndrome: Clinical Correlations and Potential Discriminatory Performance Publisher



Karbalaei Musa H ; Amin M R ; Zarei M ; Mohammadi Y ; Alani B ; Khodabandehloo F ; Mosallaei M ; Rezvankhah B
Source: Gene Reports Published:2026

Abstract

Epigenetic modifications, particularly DNA methylation, are implicated in the pathogenesis of metabolic syndrome (MetS). However, the methylation status of GFPT2, which encodes a key enzyme in the hexosamine biosynthetic pathway, remains poorly understood. Therefore, this study aimed to investigate the promoter methylation status of the GFPT2 gene in individuals with MetS and evaluate its association with clinical characteristics and its diagnostic potential. Whole blood samples were collected from 95 Iranian patients with MetS and 105 healthy controls. GFPT2 promoter methylation was quantified using the MethylQESD technique, a bisulfite conversion-independent method for the quantitative analysis of DNA methylation. Our findings revealed that GFPT2 promoter methylation was significantly higher in patients with MetS than in healthy controls (35.07 ± 19.72% vs. 25.39 ± 19.76%, P < 0.001). Receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.693 (95% CI: 0.617–0.770, P < 0.001), with a sensitivity of 78.94% and a specificity of 72.38% at the optimal cutoff value. Among patients with MetS, GFPT2 promoter methylation was positively correlated with BMI (r = 0.716, 95% CI: 0.602–0.802, P < 0.001) and waist circumference (r = 0.500, 95% CI: 0.332–0.637, P < 0.001), whereas no significant associations were observed with age, sex, smoking status, physical activity, fasting blood glucose, blood pressure, HDL cholesterol, or triglyceride levels (P > 0.05). Despite its modest discriminatory performance, GFPT2 promoter methylation may serve as a complementary biomarker within a multi-marker panel, although further studies are needed to validate its clinical utility. © 2026 Published by Elsevier Inc.