OBJECTIVE: To study the relationship of the variation of the exon 20 of leptin receptor (LEPR) gene with lipid metabolism and fat distribution in children with obesity. METHODS: One hundred and two children with simple obesity (Obesity group) and 81 healthy children (Control group) were enrolled in this study. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis were used to analyze the variation of the exon 20 of LEPR gene. The serum levels of triglyceride (TG), total cholesterol (TC), and high density lipoprotein cholesterol (HDL-C) were measured. Body mass index (BMI) and fat percentage (% fat) were calculated. RESULTS: Three genotypes of the exon 20 of LEPR gene were detected:G/G, G/A and A/A. The frequency of the gene variation at 3 057 nucleotide G→A transversion was significantly higher in the Obesity group when compared with the Control group (P<0.05). The levels of serum TG (1.8±0.5 mmol/L vs 1.0±0.4 mmol/L, P<0.01),BMI (33±5 kg/m-2 vs 25±4 kg/m-2, P<0.05) and % fat (30±8 vs 20±3, P<0.01) in obese children with A/A genotype were higher than those of the G/G genotype ones,but the level of serum HDL was lower than that of the G/G genotype patients (1.08±0.23 mmol/L vs 1.38±0.22 mmol/L, P<0.01). As to the G/A genotype patients, only their serum TG levels were higher than those of the G/G genotype ones (1.6±0.4 mmol/L vs 1.0±0.4 mmol/L, P<0.05). The electrocardiography showed the changes of ST segment and T wave in parts of A/ A genotype patients with hyperlipoidemia. CONCLUSIONS: There were polymorphisms in children with obesity and these may affect the lipid metabolism and the fat distribution. The study provided theoretic evidence for the early interference of childhood obesity.