The goal of this study is to determine whether cardiovascular risk and the methylenetetrahydrofolate reductase 677 C->T polymorphism (MTHFR), an enzyme involved in folate metabolism and in epigenetics, are linked in morbidly obese non-diabetic adolescents. One-hundred and thirteen obese (BMI = 39.1 ± 6.4 kg/m(2)) adolescents aged 14.4 ± 1.5 years were investigated before entering a weight reduction program. Information on growth obtained from individual health records was available at birth (n = 107), 1 (n = 102), 2 (n = 106), 4 (n = 91) and 8 (n = 73) years of age. Fifty-nine subjects were heterozygote (CT, 52.2%) and 8 were homozygote for the mutation (TT, 7.0%). Birth weights were lower in TT (2.95 ± 0.48 kg, p = 0.004) than in CC (3.34 ± 0.43 kg) and CT (3.38 ± 0.50 kg) subjects, as well as birth lengths (CC: 0.50 ± 0.02 m, CT : 0.50 ± 0.02 m, TT: 0.47 ± 0.03 m, p = 0.01). These differences persisted until 1 year of age. Median and mean fasting glycaemia were similar. Insulin levels were higher in TT (median: 26.4 UI/mL) than in CC (median: 15.0 UI/mL) or CT (median: 16.0 UI/mL) (p = 0.017) subjects, as well as HOMA IR (p = 0.04). Body composition, blood pressure, plasma lipids, homocysteine and leptin concentrations were similar among the three genotypes in both boys and girls. The common 677 C->T mutation seems therefore to represent a link between altered early growth and enhanced degree of insulin resistance that occurs later in obese adolescents.