Genetic basis for multimodal relationship between apolipoprotein (a) size and lipoprotein (a) concentration in...

The reported general inverse relationship between apolipoprotein (a) (apo(a)) size and plasma lipoprotein (a) (Lp(a)) concentrations was further characterized using 927 samples taken from members of 42 Mexican-American families. When all samples were displayed in a scatter plot of apo(a) size versus natural log of Lp(a) concentration, the expected inverse relationship was observed (r2 = 0.24). However, the scatter plot revealed a multimodal pattern with at least two distinct modes of the inverse relationship between apo(a) size and Lp(a) concentration. Plots of 148 single-banded samples also showed the multimodal pattern, indicating that this pattern did not result from a difference between double- and single-banded samples. Also measured was the Lp(a) concentration associated with each of 508 apo(a) isoforms in samples from 254 double-banded phenotype individuals. These separated isoforms also showed the multimodal pattern. Using pedigree information, 29 different alleles were identified which were found in three or more family members. About 85% of variation in Lp(a) was explained by allele information, suggesting a genetic basis for the multimodal pattern. Thus, the data demonstrate at least two series of apo(a) alleles that have distinct relationships between apo(a) size and Lp(a) concentration.