Genetics
ApoE genotype has opposite effects on CETP and HDL-cholesterol responses to dietary cholesterol (J Lipid Res 1993)
Original title: Cholesteryl ester transfer protein and high density lipoprotein responses to cholesterol feeding in men: relationship to apolipoprotein E genotype
Thirty young men with different apoE genotypes (5 E3/2, 11 E3/3, 14 E4/3) completed a randomized crossover comparing a low-cholesterol diet (80 mg/1000 kcal) with a high-cholesterol diet (320 mg/1000 kcal) to test whether apoE genotype modifies the lipoprotein response to dietary cholesterol. On the high-cholesterol diet, total cholesterol, LDL-cholesterol, HDL-cholesterol, and HDL2-cholesterol rose by 15%, 21%, 7%, and 23% respectively across all genotypes combined (P < 0.001 each), and the LDL-cholesterol response did not differ by genotype. However, the HDL-cholesterol increase varied significantly by apoE genotype (E3/2: no change, E3/3: +4%, E4/3: +12%, P < 0.05), while the CETP response to cholesterol feeding varied in the opposite direction (E3/2: +37%, E3/3: +18%, E4/3: +9%, P < 0.05). The authors conclude that apoE genotype has significant, opposite effects on plasma CETP and HDL-cholesterol responses to dietary cholesterol in men.
Original abstract
The apolipoprotein (apo) E isoform is an important determinant of the plasma lipoprotein distribution of apoE and of the metabolism of apoE-containing lipoproteins. We have determined the effects of apoE genotype on the plasma lipoprotein response to cholesterol feeding in 30 young normal male subjects (5 E3/2, 11 E3/3, 14 E4/3) under rigorously controlled dietary conditions. Two diets, differing only in cholesterol content (low cholesterol (LC): 80 mg cholesterol/1000 kcal and high cholesterol (HC): 320 mg cholesterol/1000 kcal), were compared using a random crossover design. At the end of the HC as compared to the LC period, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and HDL2-C increased by an average of 15%, 21%, 7%, and 23%, respectively, for the three genotype groups combined (P < 0.001 for each). The LDL-C response to dietary cholesterol did not differ among the apoE genotypes. However, the increase in HDL-C varied significantly according to the apoE genotype (E3/2: 0 change, E3/3: +4%, E4/3: +12%; P < 0.05). The plasma cholesteryl ester transfer protein (CETP) response to cholesterol feeding also differed amongst the three apoE genotype groups (E3/2: +37%, E3/3: +18%, E4/3: +9%) (P < 0.05). ApoE genotype has significant and opposite effects on plasma CETP and HDL-C responses to dietary cholesterol in men.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.