Effects of the apolipoprotein E polymorphism on uptake and transfer of cell-derived cholesterol in plasma

J Clin Invest. 1995 Dec;96(6):2693-701. doi: 10.1172/JCI118336.


The reverse cholesterol transport is initiated by the uptake of cholesterol into minor subfractions of high density lipoproteins (HDL) which contain either apolipoprotein (apo) A-I or apoE as their only apolipoproteins. From these initial acceptors, which are termed prebeta1-LpA-I and gamma-LpE, respectively, cell-derived cholesterol is transferred to LDL via the bulk of HDL termed alpha-LpA-I. In this study we analyzed the effect in plasma of the genetically determined apoE polymorphism on the formation of gamma-LpE, uptake and transfer of cell-derived cholesterol to LDL. Gamma-LpE was immunologically detectable in plasmas of individuals carrying at least one apoE3-allele but not in apoE3-free plasmas. During one minute incubation with [3H]cholesterol-labeled fibroblasts, gamma-LpE of plasmas from apoE3/3 subjects accumulated 7 and 13-fold more radioactivity than the respective fractions in plasmas from apoE2/2- and apoE4/4-subjects, respectively. Totally, 30% less [3H]cholesterol was released into plasmas of apoE2/2 and apoE4/4-individuals as compared with plasmas of apoE3/3-subjects. Moreover, plasmas of apoE3/3 individuals accumulated 50% and 65% more cell-derived [3H]cholesterol in alpha-LpA-I2 than plasmas of apoE4/4 and apoE2/2-subjects, respectively. These results indicate that the apoE-polymorphism is an important determinant of the uptake and transfer of cell-derived cholesterol in plasma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein A-I / isolation & purification
  • Apolipoproteins / blood
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / isolation & purification
  • Cells, Cultured
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Fibroblasts / metabolism
  • Humans
  • Phenotype
  • Polymorphism, Genetic*
  • Skin / metabolism
  • Sphingomyelin Phosphodiesterase
  • Triglycerides / blood
  • Type C Phospholipases


  • Apolipoprotein A-I
  • Apolipoproteins
  • Apolipoproteins E
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Triglycerides
  • Cholesterol
  • Type C Phospholipases
  • Sphingomyelin Phosphodiesterase