Biochemical, clinical, genetic and metabolic studies of hyperapo-beta-lipoproteinaemia.

Hyperapo-beta-lipoproteinaemia is a common lipoprotein disorder characterized by an elevated plasma level of the major apolipoprotein, B (apoB) of low-density beta lipoproteins (LDL), combined with a low ratio of LDL cholesterol to LDL apoB. Hyperapo-beta-lipoproteinaemia is due to the overproduction of LDL apoB that results from an enhanced synthesis of very low-density (pre-beta) lipoprotein (VLDL) in liver. The plasma levels of high-density (alpha) lipoprotein (HDL) and its major apolipoprotein, A-I, are often low in hyperapo-beta-lipoproteinaemia. Hyperapo-beta-lipoproteinaemia is often familial and aggregates in children and adults from families with premature coronary artery disease. The precise defect(s) that cause hyperapo-beta-lipoproteinaemia are not known. In a family with premature coronary artery disease and hyperapo-beta-lipoproteinaemia, a mutation in codon 4046 in exon 29 of the apolipoprotein B gene, a CGG to TGG transition produced a change from arginine, a positively charged amino acid, to tryptophan, a hydrophobic amino acid, at position 4,019 of the mature apolipoprotein B protein. Decreased incorporation of free fatty acids into triglycerides of adipocytes has been described in vitro, and in vivo studies suggested a defect in clearance of postprandial lipoproteins associated with decreased uptake of plasma free fatty acids.