Background & aimsA common G-to-A transition located 75 base pairs upstream (rs670) from transcription start site of the APOA1 gene has been related with some metabolic parameters. Our aim was to analyze the effects of rs670 APOA1 gene polymorphism on lipid profile and metabolic changes after two different hypocaloric diets. Methods282 obese subjects were randomly allocated during 12 weeks (Diet HF – high fat diet vs. Diet LF – low fat diet). Anthropometric and biochemical status were evaluated. ResultsBody mass index, weight, fat mass, waist circumference, systolic blood pressure, leptin levels and waist circumference decreased in all patients in average after both diets. In A allele carriers after 12 weeks with both diets, insulin levels (Delta diet HF: −5.3 + 1.2 UI/L; P = 0.02 and Delta diet LF: −5.8 + 1.3 UI/L; P = 0.02) and HOMA-IR (Delta diet HF: −2.9 + 0.8 units; P = 0.01 and Delta diet LF: −2.2 + 0.9 units; P = 0.03) improved in a significant way. With the low fat diet, A allele carriers showed a statistical improvement in HDL-cholesterol levels (Delta: 4 + 1 mg/dl; P = 0.03). ConclusionsOur study showed the association of rs670 ApoA1 polymorphism with a decrease of insulin resistance induced by both diets and provided additional evidence on HDL-cholesterol increase after a LF hypocaloric diet in A allele carriers.