Apolipoprotein B signal peptide polymorphism and plasma LDL-cholesterol response to low-calorie diet

OBJECTIVE: To assess the effect of the apolipoprotein B Ins/Del signal peptide. Polymorphism on plasma lipid levels in overweight subjects before and after a low-calorie diet. DESIGN: Diet intervention study (25% reduction in energy intake during 2.5 months) in relation to genetic factors. SUBJECTS: A total of 231 unrelated patients (146 women/85 men) recruited on the basis of body mass index (BMI) greater than or equal to25 kg/m(2). MEASUREMENTS: BMI, waist to hip ratio, blood lipids and lipoproteins, at entry and after 2.5 months, determination of apo B Ins/Del genotypes. RESULTS: On spontaneous diet, subjects carrying the Del allele had higher LDL-cholesterol (Del/Del: 3.97 +/- 0.62 mmol/l; Ins/Del: 3.87 +/- 1.01 mmol/l; Ins/Ins: 3.61 +/- 0.88 mmol/l) ( P = 0.038). When submitted to low-calorie diet, subjects with Del/Del genotypes reduced their LDL-cholesterol (-16.8%) more than subjects with Ins/ Del or Ins/Ins (-4.7% and +0.9%, respectively) ( P = 0.001). CONCLUSION: In overweight or obese people, the response of plasma LDL-cholesterol levels to low-calorie diet is modulated by genetic variation at the apo B locus. Overweight subjects with the Del allele of the apo B signal peptide polymorphism are predisposed to high LDL cholesterol levels but their LDL cholesterol responds well to diet. These results demonstrate the importance of the interaction between genes and nutritional environment in the determination of the lipid levels.