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 gene tically controlled. Apolipoprotein (Apo) E polymorphism has been shown to i nfluence basal plasma lipid levels and the response to dietary changes in n ormolipidemic 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 res ponse to diet in subjects with familial hypercholesterolemia (FH) is also v ariable, 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 F H heterozygotes (44 women and 25 men). Subjects were studied at baseline (a fter consuming for I month a diet with 35% fat [10% saturated] and 300 mg c holesterol) 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 fre quency distribution of apo E alleles was similar to that described in the g eneral Spanish population: 0.0724 for the E2 allele, 0.0724 for E4 and 0.85 51 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 subj ects and no apoE allele-related differences were identified As in non-FH su bjects, 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 sup ports the hypothesis that the impact of genetic defects at the low density lipoprotein receptor (LDLR) locus in FH subjects prevails over any influenc e on the part of ApoE polymorphism. (C) 2000, Medikal Press.