Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a]

Abstract

(16,18,19). In several studies, small apo[a] sizes have been associated with cardiovascular disease (12,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and associations between small apo[a] and cardiovascular disease have remained significant after adjustment for apo [a] level (12, 24-28 Besides the size variation, a C/T polymorphism in the promoter region of the gene (193) and an upstream pentanucleotide repeat (PNR) polymorphism, with 5-12 TTTTA repeats starting at 21,373, have been described in addition to other single-nucleotide polymorphisms (31-38). In transfection experiments, the T nucleotide was associated with lower apo[a] formation as a result of the introduction of a novel start codon (31). In vitro studies of the PNR polymorphism have demonstrated less transcriptional activity for constructs containing nine compared with eight TTTTA repeats (39). In studies in

ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in African Americans: the Harlem-Basset Study

“…1, among African Americans, there was a stepwise increase in Lp[a] levels from e2 to e3 to e4 carriers. Thus, African American e2 carriers had significantly lower levels (17). As seen in Fig.…”

“…This study was undertaken to address a possible impact of apoE genotypes on allele-specific apo[a] levels. Previous studies have shown the following: 1) apoE genotypes have a wide impact on plasma lipoprotein levels (21, 38); 2) apoE allele frequency differs between African Americans and Caucasians (22,23,38); 3) plasma Lp[a] levels differ between African Americans and Caucasians (10-14); and 4) the difference in allele-specific apo[a] levels for larger apo [a] size between African Americans and Caucasians is unexplained (17). In our population, we have shown that African Americans have higher allele-specific apo[a] levels compared with Caucasians.…”

“…Importantly, Africans as well as African Americans have substantially higher Lp[a] levels than do Caucasians or Asians, adjusting for apo [a] sizes (15,16). Recently, we demonstrated that for small apo[a] sizes, differences in allele-specific apo[a] levels between African Americans and Caucasians were explained by allelic interactions and by an upstream pentanucleotide repeat polymorphism (17). However, differences in allele-specific apo[a] levels remain unexplained for larger apo [a] sizes.…”

“…As African Americans have higher lipoprotein [a] (15,18,19). Furthermore, as described above, we and others have identified several genetic variations that affect allele-specific apo[a] levels (8,16,17,20). Genetic variability of apolipoprotein E (apoE) is a major determinant of plasma lipoprotein levels (21), and furthermore, apoE genotype frequencies differ between African Americans and Caucasians (22,23).…”

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol

“…The study design has been described (28,29). Briefly, 648 patients, 401 men and 247 women, self-identified as Caucasian (n 5 344), African American (n 5 232), or other (n 5 72) were enrolled.…”