Integrated role of two apoliprotein E polymorphisms on apolipoprotein B levels and coronary artery disease in a biethnic population

Abstract

Background: Apolipoprotein E (ApoE) plays a major role in lipoprotein metabolism and genetic variability of ApoE confers susceptibility to coronary artery disease (CAD). Beyond variability in the coding region, promoter polymorphisms in the ApoE gene impact on ApoE transcription.

Methods: We determined the ApoE - 491 A/T promoter polymorphism, ApoE isoforms, lipid and lipoprotein levels, and CAD risk factors in 313 Caucasians and 215 African Americans.

Results: Caucasians had a lower ApoE T allele frequency compared to African Americans (18.1% vs. 32.3%, P < 0.05). Among T/* carriers, ApoB levels were significantly lower in Caucasians, but significantly higher among African Americans, in both cases compared to A/A homozygotes (P = 0.017, and P = 0.012). For a given -491A/T genotype, levels of atherogenic lipoproteins differed across ApoE2/E3/E4 isoforms among African Americans, but not Caucasians, as T/* carriers with ApoE4 had significantly higher ApoB levels compared to T/* carriers with ApoE2 (P = 0.010). Among patients with CAD, Caucasian A/A homozygotes and African American T/* carriers had higher ApoB levels compared to the same genotype without CAD (P = 0.007, P = 0.049, respectively).

Conclusions: We observed an ethnicity-specific variability in ApoB levels across the ApoE - 491 A/T polymorphism and a modulatory impact on this pattern by ApoE2/E3/E4 isoforms.

FIG. 1.

Apolipoprotein B (ApoB) and ApoA-I levels in subjects with (+) and without (−) coronary artery disease (CAD) across ApoE −491 A/T genotypes in Caucasians and African Americans. (*) P < 0.05.

FIG. 2.

Distribution of the apoliprotein E (ApoE) −491 A/T polymorphisms on ApoE2/E3/E4 isoforms across Caucasian and African American ethnicities. Distribution of the A/A homozygotes (A), and T/* carriers (B) among the ApoE2/E3/E4 isoforms across the ethnicity.