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 di fferent apolipoprotein(a) (apo(a)) alleles, conditions were establishe d whereby phenotyping immunoblots could be used to estimate the concen tration of Lp(a) associated with the constituent apo(a) isoforms. In t hese studies 28 distinct isoforms were identified, each differing by a single kringle IV unit. Tracking the isoforms through 10 families sho wed that there could be up to 200-fold difference in the Lp(a) concent ration associated with the same-sized isoform produced from different alleles. In contrast there was typically < 2.5-fold variation in the L p(a) concentration associated with the same allele. However, there wer e 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 supe rimposed upon the other factors that determine Lp(a) concentration. In heritance of familial hypercholesterolemia or familial-defective apoB( 100) had little consistent effect upon Lp(a) concentration. In both th e families and in other unrelated individuals the distribution of isof orms and their associated concentrations provided evidence for the pre sence of at least two and possibly more subpopulations of apo(a) allel es with different sizes and expression.