Effects of a frequent apolipoprotein E isoform, ApoE4Freiburg (Leu28-->Pro), on lipoproteins and the prevalence of coronary artery disease in whites

Arterioscler Thromb Vasc Biol. 1999 May;19(5):1306-15. doi: 10.1161/01.atv.19.5.1306.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Amino Acid Substitution*
  • Apolipoprotein E4
  • Apolipoproteins / blood
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / isolation & purification
  • Blood Protein Electrophoresis
  • Chylomicrons / blood
  • Comorbidity
  • Coronary Disease / blood
  • Coronary Disease / epidemiology*
  • Coronary Disease / genetics
  • Eating
  • European Continental Ancestry Group / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Germany / epidemiology
  • Humans
  • Hyperlipoproteinemias / blood
  • Hyperlipoproteinemias / epidemiology
  • Hyperlipoproteinemias / genetics
  • Isoelectric Focusing
  • Lipids / blood
  • Lipoproteins / metabolism
  • Lipoproteins, HDL / metabolism
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics
  • Odds Ratio
  • Phenotype
  • Polymorphism, Restriction Fragment Length
  • Prevalence
  • Protein Isoforms / genetics*
  • Protein Isoforms / isolation & purification
  • Receptors, LDL / metabolism
  • Risk Factors
  • Triglycerides / metabolism

Substances

  • Apolipoprotein E4
  • Apolipoproteins
  • Apolipoproteins E
  • Chylomicrons
  • Lipids
  • Lipoproteins
  • Lipoproteins, HDL
  • Protein Isoforms
  • Receptors, LDL
  • Triglycerides
  • apolipoprotein E4 (Freiburg)