HyperapoB: A pleiotropic phenotype characterized by dense low-density lipoproteins and associated with coronary artery disease

HyperapoB, a lipoprotein phenotype characterized by increased numbers of small, dense, low-density lipoproteins (LDL), is strongly associated with coronary artery disease (CAD). Patients with hyperapoB may be normolipidemic, hypertriglyceridemic, or, when the number of LDL particles increases sufficiently, hypercholesterolemic. Concentrations of high-density lipoprotein (HDL) and its major apolipoprotein, apo A-I, are often low in plasma of patients with hyperapoB. The increased number of dense LDL in hyperapoB is due to increased LDL synthesis, secondary to increased synthesis of very-low-density lipoproteins (VLDL) and apo B. HyperapoB may be a dominant trait, although the existence of a common recessive allele at a very high frequency has not been excluded. The expression of hyperapoB appears delayed, but the phenotype is commonly found in children referred to specialty lipid clinics because of a family history of premature CAD. Published data suggest a biochemical, genetic, and metabolic relationship between hyperapoB, familial combined hyperlipidemia, and the dense LDL subclass patterns described in Mormon families. The biochemical and genetic basis for the overproduction of VLDL apo B is under further study, both molecular investigations of the apo B gene and studies of free fatty acid, triglyceride, and HDL metabolism.