Methylation Analysis of Phospho1 and Acaca Gene Promoters in Whole Blood Samples: Insights Into Metabolic Syndrome and Associated Factors Publisher



Rezvankhah B ; Ehtesham N ; Hajali MH ; Sadeghi S ; Alani B ; Kenarangi T ; Mosallaei M ; Mirjani R
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Purpose: Recent advances in the rapidly evolving field of epigenetics have uncovered a complex network of interactions between epigenetic processes and human diseases, particularly metabolic syndrome (MetS). This study sought to evaluate blood-based DNA methylation changes in PHOSPHO1 and ACACA, two genes involved in glucolipid metabolism, comparing healthy individuals with those diagnosed with MetS. Methods: We conducted a comprehensive analysis of whole blood DNA methylation utilizing the MethyQESD technique on selected genes from 90 MetS patients and 90 healthy controls of Iranian descent. Additionally, we examined the correlation between the DNA methylation levels of these two genes and various anthropometric and biochemical parameters related to metabolic profiles. Results: Our findings indicated a reduction in DNA methylation for PHOSPHO1 and an increase for ACACA in patients relative to controls; however, these differences were not statistically significant (P: 0.088 and 0.054 for PHOSPHO1 and ACACA, respectively). Notably, when considering FBS levels, significant differences in DNA methylation levels were observed between patients with normal and abnormal FBS levels (P < 0.001). Furthermore, the DNA methylation level of PHOSPHO1 showed an inverse relationship with BMI and FBS, while it was directly correlated with HDL-c levels; similarly, the DNA methylation level of ACACA was negatively correlated with HDL-c and positively correlated with FBS. Conclusions: While our findings do not support the use of PHOSPHO1 and ACACA DNA methylation levels as biomarkers, they may contribute to a deeper understanding of the mechanisms underlying MetS and aid in the development of innovative therapeutic strategies. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.