Effects of a frequent apolipoprotein E isoform, ApoE4(Freiburg) (Leu28 -> Pro), on lipoproteins and the prevalence of coronary artery disease in whites

Different isoforms of apoE modulate the concentrations of plasma lipoprotei ns and the risk for atherosclerosis. A novel apoE isoform, apoE4(Freiburg), was detected in plasma by isoelectric focusing because its isoelectric poi nt is slightly more acidic than that of apoE4. ApoE4(Freilburg) results fro m a base exchange in the APOE4 gene that causes die replacement of a leucin e by a proline at position 28. Analysis of the allelic frequencies in white s in southwestern Germany revealed that this isoform is frequent among cont rol subjects (10:4264 alleles) and is even more frequent in patients with c oronary artery disease (21:2874 alleles; P=0.004; adjusted odds ratio, 3.09 ; 95% confidence interval, 1.20 to 7.97). ApoE4(Freiburg) affects serum lip oproteins by lowering cholesterol, apoB, and-apoA-I compared with apoE4 (P < 0.05). Our 4poE4(Freiburg) homozygotes suffered from various phenotypes o f hyperlipoproteinemia (types IIa, IIb, IV, and V). In vitro binding studie s excluded a binding defect of apoE4(Freilburg), and in vivo studies exclud ed an abnormal accumulation of chylomicron remnants. ApoE4(Freiburg) and ap oE4 accumulated to a similar extent in triglyceride-rich lipoproteins. HDLs , however, contained about 40% less apoE4,,,, than apoE4. In conclusion, ou r data indicate that apoE4(Freiburg) exerts its possible atherogenic proper ties by affecting the metabolism of triglyceride-rich lipoproteins and HDL.