Effects of a frequent apolipoprotein E isoform, ApoE4Freiburg (Leu28-->Pro), on lipoproteins and the prevalence of coronary artery disease in whites.
Different isoforms of apoE modulate the concentrations of plasma lipoproteins and the risk for atherosclerosis. A novel apoE isoform, apoE4Freiburg, was detected in plasma by isoelectric focusing because its isoelectric point is slightly more acidic than that of apoE4. ApoE4Freiburg results from a base exchange in the APOE4 gene that causes the replacement of a leucine by a proline at position 28. Analysis of the allelic frequencies in whites in southwestern Germany revealed that this isoform is frequent among control subjects (10:4264 alleles) and is even more frequent in patients with coronary artery disease (21:2874 alleles; P=0.004; adjusted odds ratio, 3.09; 95% confidence interval, 1.20 to 7.97). ApoE4Freiburg affects serum lipoproteins by lowering cholesterol, apoB, and apoA-I compared with apoE4 (P<0.05). Our 4 apoE4Freiburg homozygotes suffered from various phenotypes of hyperlipoproteinemia (types IIa, IIb, IV, and V). In vitro binding studies excluded a binding defect of apoE4Freiburg, and in vivo studies excluded an abnormal accumulation of chylomicron remnants. ApoE4Freiburg and apoE4 accumulated to a similar extent in triglyceride-rich lipoproteins. HDLs, however, contained about 40% less apoE4Freiburg than apoE4. In conclusion, our data indicate that apoE4Freiburg exerts its possible atherogenic properties by affecting the metabolism of triglyceride-rich lipoproteins and HDL.
D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D053327:Apolipoprotein E4; D001053:Apolipoproteins / Q000097:blood; D001057:Apolipoproteins E / Q000235:genetics* / Q000302:isolation & purification; D001797:Blood Protein Electrophoresis; D002914:Chylomicrons / Q000097:blood; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D004435:Eating; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D007525:Isoelectric Focusing; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D020033:Protein Isoforms / Q000235:genetics* / Q000302:isolation & purification; D011973:Receptors, LDL / Q000378:metabolism; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism; D044465:White People / Q000235:genetics*