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Aim: Obesity and its metabolic complications are increasing in childhood and extend to adulthood. The aims of this study were to assess the prevalence of metabolic syndrome (MS) in a sample of Egyptian adolescent girls and investigate its association with apolipoprotein E., Methods: A cross-sectional study design was used, including 200 Egyptian adolescent girls aged between 12 and 18 years. They were subjected to blood pressure (BP) measurement, anthropometric measurements (weight, height and waist circumference (WC)), laboratory investigations (fasting glucose and lipid profile) and molecular analysis (Apo E)., Results: Overweight/obese girls were suffering significantly, more than normal-weight girls, from hypertension (66.7 vs. 40.8%), diabetes diagnosed by elevated fasting blood glucose (46.7 vs. 31.2%) and low high-density lipoprotein (HDL) (64 vs. 59.2%). Girls with MS had significantly higher values of body mass index Z-score, WC, BP, cholesterol and triglycerides and significantly lower HDL. Allele E3 (59.1 vs. 55.1%) was more frequent among girls with MS, while allele E4 (41 vs. 36.4) was more frequent among girls without MS. MS was the most prominent among girls with the E3/E4 genotype (35.7%), who had the highest frequency of elevated cholesterol, triglycerides, low-density lipoprotein and blood glucose, while girls with the E2/E4 genotype, which was rare among both groups, had the highest frequency of elevated BP (68.8%) and low HDL (71.4%)., Conclusion: MS was significantly more prominent among overweight/obese adolescent girls with the E3/E4 genotype, who had the highest frequency of disturbed lipid profile and blood glucose., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)