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The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. <i>FTO</i> (<i>FTO</i> alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene <i>PLAG1</i> (<i>PLAG1</i> zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the <i>FTO</i> gene in obese children and in patients with documented insulin resistance. Higher <i>FTO</i> expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). <i>FTO</i> methylation correlated positively with WC and BF_kg. Increase in <i>PLAG1</i> expression was associated with higher BF%. Our results indicate that the <i>FTO</i> gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.