Effect of apolipoprotein E polymorphism on serum lipid response to the separate modification of dietary fat and dietary cholesterol

Background: The magnitude of the influence of the apolipoprotein (apo) E ge notype on the lipid response to different cholesterol-lowering diet modific ations has been controversial. Objective: The aim of the study was to investigate the effect of apo E geno type on serum lipid response to the separate modification of dietary fat an d cholesterol. Design: A prospective study design with the 3 main apo E genotype groups (3 /3, 3/4, and 4/4; n = 15 in each group) was used. Groups were matched for s ex, age, body mass index, menopausal status, and baseline serum cholesterol concentration. Subjects followed 3 different diets in fixed order: 1) a st andardized baseline diet (38% fat, 300 mg cholesterol/d), 2) a modified Nat ional Cholesterol Education Program (NCEP) diet (34% fat, 265 mg cholestero l/d), and 3) the modified NCEP diet + cholesterol (566 mg cholesterol/d). S ubjects were middle-aged (50.9 +/- 8.0 y) and mildly hypercholesterolemic ( 6.55 +/- 1.05 mmol/L). Results: The genotype groups differed in their total cholesterol response t o the NCEP diet; the mean (95% CI) decrease being greatest, -14.1% (-19.8%, -8.6%),in subjects with apo E genotype 4/4 (P = 0.03, analysis of variance ). The increase in total cholesterol after addition of 300 mg cholesterol w as also greatest in subjects with apo E 4/4 [10.4% (5.8%, 15.1%)] (P = 0.03 , analysis of variance). Conclusions: Apo E genotype modified the lipid response to changes in both dietary fat and cholesterol in mildly hypercholesterolemic subjects; the re sponse was greatest in subjects with apo E genotype 4/4 and even a moderate increase in dietary cholesterol resulted in a 10% elevation in serum total cholesterol in them.