Variation in lipoprotein(a) concentration associated with different apolipoprotein(a) alleles

Plasma lipoprotein(a) (Lp(a)) concentrations vary considerably between individuals. To examine the variation for products of the same and different apolipoprotein(a) (apo(a)) alleles, conditions were established whereby phenotyping immunoblots could be used to estimate the concentration of Lp(a) associated with the constituent apo(a) isoforms. In these studies 28 distinct isoforms were identified, each differing by a single kringle IV unit. Tracking the isoforms through 10 families showed that there could be up to 200-fold difference in the Lp(a) concentration associated with the same-sized isoform produced from different alleles. In contrast there was typically < 2.5-fold variation in the Lp(a) concentration associated with the same allele. However, there were four occasions where the concentration associated with a particular allele was reduced below the typical range from one generation to the next. A nonlinear, inverse trend with isoform size was apparently superimposed upon the other factors that determine Lp(a) concentration. Inheritance of familial hypercholesterolemia or familial-defective apoB100 had little consistent effect upon Lp(a) concentration. In both the families and in other unrelated individuals the distribution of isoforms and their associated concentrations provided evidence for the presence of at least two and possibly more subpopulations of apo(a) alleles with different sizes and expression.