Abstract 1346: Genetic Determinants of Lipoprotein(a): ApoE Genotype Predicts Allele-Specific apo(a) Levels in African Americans
Background: Lipoprotein(a), Lp(a), is a cardiovascular risk factor. Lp(a) levels are largely determined by apo(a), which has a pronounced size heterogeneity. Plasma Lp(a) levels are higher among African Americans than Caucasians, but this difference is not explained by differences in apo(a) size distribution.
Objective: As apoE genotype predicts plasma lipoprotein levels, and apoE allele frequencies differ between African Americans and Caucasians, we investigated the effects of the apoE gene on allele-specific apo(a) levels across ethnicity.
Methods: We determined apo(a) sizes, allele-specific apo(a) levels and apoE genotypes in 167 African Americans and 259 Caucasians.
Results: African Americans, but not Caucasians, with apo ϵ2 (E2/2, E2/3) genotype had significantly lower levels of Lp(a) compared to those with apo ϵ4 (E4/3, E4/4) (31 vs. 47 mg/dl; P=0.033). We hypothesized that the differences in Lp(a) levels in African Americans across apoE genotypes might be due to either; 1) a different distribution pattern of apo(a) alleles, or 2) a difference in allele specific apo(a) levels. No difference was observed in apo(a) allele distribution across apoE genotypes for either African Americans or Caucasians, and allele-specific levels for smaller size apo(a) (≤26 K4 repeats) was similar across apoE genotypes in both ethnic groups. Among African Americans with larger size apo(a) (>26 K4 repeats), the allele-specific apo(a) level was significantly lower among ϵ2-carriers compared to ϵ3- or ϵ4-carriers (12.2 vs. 22.7 and 22.2 mg/dl, P<0.005), respectively. In contrast, there was no significant difference in allele specific apo(a) levels across apoE genotype among Caucasians with larger size apo(a) alleles.
Conclusion: The main novel findings in our study are as follows:
African American apo ϵ2-carriers, compared to ϵ3-or ϵ4-carriers, had lower allele-specific apo(a) levels for larger apo(a) sizes;
observed African American-Caucasian differences were partially explained for larger apo(a) sizes by apoE genotype.
These findings implicate an interaction between apoE genotype and Lp(a) in African Americans, and suggest that in this ethnic group, apoE-mediated pathways may influence Lp(a) levels through apo(a) molecular properties.