Apolipoprotein E phenotype and lipoprotein(a) in familial hypercholesterolaemia implication for lipoprotein(a) metabolism

Abstract

The mechanisms regulating plasma levels of lipoprotein(a) [Lp(a)] are largely unknown. A two- to three-fold increase in Lp(a) levels in patients with familial hypercholesterolaemia (FH) has implied that LDL receptor activity may be an important factor in determining plasma Lp(a) levels, as it is in determining low-density lipoprotein (LDL) cholesterol concentration. Common apolipoprotein E (apoE) variants also affect plasma LDL cholesterol levels. We therefore examined the effect of the common apoE variants on plasma Lp(a) levels in 149 patients with heterozygous FH. Patients with the apoE2 allele (n = 11) had significantly higher plasma levels of LDL cholesterol compared to those with a apoE3E3 phenotype, while patients with the apoE4 isoform had similar levels. However, there was a significant effect of the apoE2 allele in lowering Lp(a) levels, compared to the apoE3E3 group. The median Lp(a) concentration in patients possessing an apoE2 isoform was 13.1 mg/dl below the median, while in those with an apoE4 allele the median Lp(a) levels were 4.13 mg/dl higher. There was a marked inverse correlation between plasma Lp(a) and LDL cholesterol concentration in the FH patients carrying the apoE2 allele. Our data imply that difference in Lp(a) levels observed between FH patients with different apoE isoforms does not result from altered clearance of Lp(a) via the LDL receptor pathway, and suggest that apoE mediated hepatic up-take, or conversion, of remnant particles may be determining Lp(a) production rate.