Apolipoprotein E gene promoter 219G3T polymorphism increases LDL-cholesterol concentrations and susceptibility to oxidation in response to a diet rich in saturated fat

Background: The apolipoprotein E (APOE) gene promoter polymorphism ( 219G3T) has been associated with increased risk of myocardial infarction, premature coronary artery disease, and decreased plasma apolipoprotein E concentrations. Objective: We aimed to determine in healthy subjects whether this polymorphism modifies the susceptibility of LDL to oxidation and the lipid response to the content and quality of dietary fat. Design: Fifty-five healthy men with the APOE3/E3 genotype (7 GG, 38 GT, and 10 TT) completed 3 dietary periods, each lasting 4 wk. The first was a saturated fatty acid (SFA)-rich diet [38% fat—20% SFA and 12% monounsaturated fatty acid (MUFA)—and 47% carbohydrates (CHO)], which was followed by a CHO-rich diet (30% fat— 10% SFA and 12% MUFA—and 55% CHO) or a MUFArich diet (38% fat— 10% SFA and 22% MUFA—and 47% CHO) in a randomized crossover design. At the end of each dietary period, LDL oxidation susceptibility, lipids, and lipoproteins were measured. Results: Compared with carriers of the G allele, TT subjects had a significantly (P 0.05) shorter lag time after the SFA diet. The replacement of the SFA diet by the CHO or MUFA diet induced a greater increase (P 0.05) in lag time in the TT subjects than in the GG or GT subjects. Carriers of the T allele had higher LDLcholesterol (P 0.05) and apolipoprotein B (P 0.05) plasma concentrations after the SFA diet than did GG subjects. Compared with GG subjects, carriers of the T allele had a significantly (P 0.05) greater decrease in LDL cholesterol and apolipoprotein B when they changed from the SFA to the CHO diet. Conclusion: The 219G3T polymorphism may partially explain differences in individual responses to diet. Am J Clin Nutr 2004;