Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans

Abstract

Lp[a] concentrations in nmol/L and apo[a] size isoforms, expressed in terms of the relative number of apo[a] kringle 4 (K4) repeats, were determined in 3959 whites and blacks from four U.S. communities. Plasma Lp[a] analyses were performed by an ELISA method insensitive to apo[a] size heterogeneity and apo[a] size isoforms were determined by high resolution agarose gel electrophoresis. Allele frequencies were estimated by maximum likelihood methods in order to account for the presence of null alleles and coalescence of hands on gels. The apo[a] allele frequencies and phenotype distributions differed significantly between blacks and whites (P < 0.0001). Blacks had a higher relative frequency of the intermediate alleles K4(22) through K4(28) whereas whites had a higher relative frequency of the small alleles K4(17) through K4(24) and large alleles K4(29) through K4(33). The estimated frequency of the null allele was low in both blacks (1.0%) and whites (6.7%). The Lp[a] distribution was less skewed and Lp[a] concentrations were higher in blacks than whites (mean 94 nmol/L and 48 nmol/L, median 74 nmol/L and 20 nmol/L for blacks and whites, respectively). The relationship between apo[a] size and Lp[a] concentration also differed significantly between these two racial groups. For the large polymorphs (> 31 K4 repeats) both blacks and whites exhibited uniformly low Lp[a] values. For the intermediate isoforms K4(20) through K4(30), a considerable range of Lp[a] values was evident in blacks; the median Lp[a] for each isoform increased nearly linearly as the apo[a] size decreased. In contrast in whites there was little change in median Lp[a] concentrations for isoforms K4(20) through K4(30). For the small apo[a] size (< 20 K4) both blacks and whites exhibited high median Lp[a] levels and a wide variation of Lp[a] levels. The major difference in Lp[a] levels between the two racial groups occurred in the intermediate size isoform range of K4(20) through K4(25). In conclusion, whites and blacks differ significantly in Lp[a] concentrations, allele and phenotype frequencies, and in the relationship between apo[a] size isoform and Lp[a] concentration.