Association between the DNA methylations of POMC, MC4R, and HNF4A and metabolic profiles in the blood of children aged 7–9 years

BACKGROUND Proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R), and hepatocyte nuclear factor 4 alpha (HNF4A) are closely associated with weight gain and metabolic traits. In a previous study, we demonstrated associations between the methylations of POMC, MC4R, and HNF4A and metabolic profiles at birth. However, little is known about these associations in obese children. To evaluate the clinical utility of epigenetic biomarkers, we investigated to determine whether an association exists between the methylations of POMC, MC4R, and HNF4A and metabolic profiles in blood of normal weight and overweight and obese children. METHODS We selected 79 normal weight children and 41 overweight and obese children aged 7-9 years in the Ewha Birth and Growth Cohort study. POMC methylation levels at exon 3, and MC4R and HNF4A methylation levels in promoter regions were measured by pyrosequencing. Serum glucose, total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-c), and insulin levels were analyzed using a biochemical analyzer and an immunoradiometric assay. Partial correlation and multiple regression analysis were used to assess relationships between POMC, MC4R, and HNF4A methylation levels and metabolic profiles. RESULTS Significant correlations were found between POMC methylation and HDL-c levels, and between HNF4A methylation and both TC and HDL-c levels. Interestingly, associations were found between POMC methylation status and HDL-c levels, and between HNF4A methylation status and TC levels independent of body mass index. CONCLUSIONS These findings show that POMC, MC4R, and HNF4A methylation status in the blood of children are associated with metabolic profiles. Therefore, we suggest that the DNA methylation status might serve as a potential epigenetic biomarkers of metabolic syndrome.