THE EFFECT OF GENETIC-DETERMINANTS OF LOW-DENSITY-LIPOPROTEIN LEVELS ON LIPOPROTEIN (A)

Levels of Lipoprotein(a) [Lp(a)] correlate directly with atherosclerosis risk. The Lp(a) particle is physically and chemically similar to low density lipoprotein (LDL), the main difference being the presence of apolipoprotein(a) [apo(a)] bonded to the apoB-100 moiety of LDL. Genetic variation of apo(a) primarily determines Lp(a) phenotype. However, other genetic factors may also have a role in determining Lp(a) levels. Large families provide a unique opportunity to evaluate the contribution of genetic factors to disease. In several large Utah kindreds with various genetic abnormalities of lipoprotein metabolism we determined that: 1) Lp(a) levels are associated with defects at the apoB gene; 2) Lp(a) levels are not associated with defects at the LDL-receptor gene; 3) high density lipoprotein (HDL) levels are associated with genetic variation at the apo(a) locus; and 4) the DNA sequence of the apoB-100 binding domain does not vary between siblings with high and low Lp(a) levels.