Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians

Plasma lipoprotein a] (Lpa]) concentrations are inversely associated with, and largely determined by, apolipoprotein a] (apoa]) gene size, a highly polymorphic trait. We studied if, within an individual, the smaller apoa] isoform always dominated, whether there was interaction between the two alleles, and whether these features differed between Caucasians and African Americans. We determined apoa] gene sizes, apoa] protein sizes and relative amounts, and plasma Lpa] levels in 430 individuals (263 Caucasians and 167 African Americans). Of the 397 heterozygotes with at least one detectable apoa] isoform (238 Caucasians and 159 African Americans), the larger allele dominated in 28% of Caucasians and 23% of African Americans, while the smaller allele dominated in 56% of Caucasians and 45% of African Americans. In Caucasians, dominance of the smaller allele increased with Lpa] levels, from 44% at Lpa] < or = 30 nM to 81% at Lpa] >100 nM (P < 0.0001). Dominance by the smaller allele increased with increasing size of the larger allele in both groups but with the smaller allele only in African Americans. There was no interaction between apoa] alleles within genotypes; one apoa] isoform level was not associated with the other isoform level, and isoform levels were not affected by the difference in size. More of the dominance pattern was explained by Lpa] level and apoa] genotype in African Americans than in Caucasians (29% vs. 13%). Thus, genotype influences isoform-specific Lpa] levels and dominance patterns differently in African Americans and in Caucasians.