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Journal of Lipid Research, Vol 35, 1965-1975, Copyright © 1994 by Lipid Research, Inc.


ARTICLES

Effect of apolipoprotein E phenotype on diet-induced lowering of plasma low density lipoprotein cholesterol

J Lopez-Miranda, JM Ordovas, P Mata, AH Lichtenstein, B Clevidence, JT Judd and EJ Schaefer
Lipid Metabolism Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.

The National Cholesterol Education Program (NCEP) has recommended that dietary total fat, saturated fat, and cholesterol intake be reduced to < or = 30% of calories, < 10% of calories, and < 300 mg/day, respectively (Step 1 diet) in the general population to reduce plasma low density lipoprotein (LDL) cholesterol levels and heart disease risk. We examined the LDL cholesterol-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/day of cholesterol) as compared to an average American diet (39% fat, 15% saturated fat, and 435 mg/day of cholesterol) in 128 subjects using diet periods of 4-24 weeks for each diet phase. The mean LDL cholesterol reduction was 15% in males (n = 83) and 8% in post-menopausal females (n = 45). The effect of apolipoprotein (apo) E phenotype on responsiveness was examined. LDL cholesterol lowering in males was 14% for 60 apoE3/3 subjects, 23% for 10 apoE3/4 subjects, and 16% for 13 apoE3/2 subjects. Male apoE3/4 subjects had a significantly greater LDL cholesterol reduction (P = 0.006) and a greater decrease in the LDL/HDL ratio (P = 0.047) than apoE3/3 subjects. In females, 7% lowering in LDL cholesterol was observed in 34 apoE3/3 subjects and 11% lowering was observed in 7 apoE3/4 subjects (P = 0.12). A meta-analysis of data from published studies supports this conclusion. These data indicate that apoE phenotype modulates the LDL cholesterol-lowering response to a diet meeting NCEP Step 1 criteria, and that male subjects carrying the apoE4 allele are more responsive than other subjects.
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