Effect of apolipoprotein E genotype on lipid levels and response to diet in familial hypercholesterolemia.
The response of plasma lipids to dietary fat and cholesterol is partly genetically controlled. Apolipoprotein (Apo) E polymorphism has been shown to influence basal plasma lipid levels and the response to dietary changes in normolipidemic individuals. In general, subjects carrying the E4 allele have higher basal total and low density lipoprotein cholesterol (LDL-C) plasma levels and show an increased LDL-C response to dietary manipulation. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, but the influence of apo E genotypes on their dietary response has received little attention. We studied such influence on the lipid response to the National Cholesterol Education Program type I (NCEP-I) diet in 69 FH heterozygotes (44 women and 25 men). Subjects were studied at baseline (after consuming for 1 month a diet with 35% fat [10% saturated] and 300 mg cholesterol) and after 3 months of consuming a low-fat diet. No sex-related differences were found, and results were combined for men and women. The frequency distribution of apo E alleles was similar to that described in the general Spanish population: 0.0724 for the E2 allele, 0.0724 for E4 and 0.8551 for E3. Baseline plasma lipid and lipoprotein values were not influenced by apo E genotype. The response to the NCEP-I diet was similar in all subjects and no apoE allele-related differences were identified. As in non-FH subjects, there was a nonsignificant trend towards greater LDL-C lowering in E4 (-19.3%) than in E3 (-18.2%), and E2 (-16.6%) carriers. This finding supports the hypothesis that the impact of genetic defects at the low density lipoprotein receptor (LDLR) locus in FH subjects prevails over any influence on the part of ApoE polymorphism.
Carmena-Ramón
R
R
Department of Medicine, Hospital Clínico Universitario, University of Valencia, Spain.
Real
J T
JT
Ascaso
J F
JF
Ordovás
J M
JM
Carmena
R
R
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018752:Diet, Fat-Restricted; D005260:Female; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000178:diet therapy / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol