APOLIPOPROTEIN-E PHENOTYPE AND LIPOPROTEIN(A) IN FAMILIAL HYPERCHOLESTEROLEMIA - IMPLICATION FOR LIPOPROTEIN(A) METABOLISM

The mechanisms regulating plasma levels of lipoprotein(a) [Lp(a)] are largely unknown. A two- to three-fold increase in Lp(a) levels in pati ents with familial hypercholesterolaemia (FH) has implied that LDL rec eptor activity may be an important factor in determining plasma Lp(a) levels, as it is in determining low-density lipoprotein (LDL) choleste rol concentration. Common apolipoprotein E (apoE) variants also affect plasma LDL cholesterol levels. We therefore examined the effect of th e common apoE variants on plasma Lp(a) levels in 149 patients with het erozygous FH. Patients with the apoE(2) allele (n = 11) had significan tly higher plasma levels of LDL cholesterol compared to those with a a poE(3)E(3) phenotype, while patients with the apoE(4) isoform had simi lar levels. However, there was a significant effect of the apoE(2) all ele in lowering Lp(a) levels, compared to the apoE(3)E(3) group. The m edian Lp(a) concentration in patients possessing an apoE(2) isoform wa s 13.1 mg/dl below the median, while in those with an apoE(4) allele t he median Lp(a) levels were 4.13 mg/dl higher. There was a marked inve rse correlation between plasma Lp(a) and LDL cholesterol concentration in the FH patients carrying the apoE(2) allele. Our data imply that d ifference 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) productio n rate.