Type III hyperlipoproteinemia associated with apolipoprotein E phenotype E3/3. Structure and genetics of an apolipoprotein E3 variant

J Clin Invest. 1989 Apr;83(4):1095-101. doi: 10.1172/JCI113988.


A family has been described in which type III hyperlipoproteinemia is associated with apo E phenotype E3/3 (Havel, R. J., L. Kotite, J. P. Kane, P. Tun, and T. Bersot. 1983. J. Clin. Invest. 72:379-387). In the current study, the structure of apo E from the propositus of this family was determined using both protein and DNA analyses. The propositus is heterozygous for two different apo E alleles, one coding for normal apo E3 and one for a previously undescribed variant apo E3 in which arginine replaces cysteine at residue 112 and cysteine replaces arginine at residue 142. Apo E gene analysis of nine other family members spanning four generations indicated that only those five members having type III hyperlipoproteinemia possess the variant apo E3. Like the propositus, all five are heterozygous for this variant, suggesting that the disorder in this family is transmitted in a dominant fashion. The variant apo E3 was defective in its ability to bind to lipoprotein receptors, and this functional defect probably contributes to the expression of type III hyperlipoproteinemia in this family.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / isolation & purification
  • Apolipoproteins E / metabolism
  • Base Sequence
  • Child
  • Female
  • Genetic Testing
  • Genetic Variation*
  • Humans
  • Hyperlipoproteinemia Type IV / diagnosis
  • Hyperlipoproteinemia Type IV / genetics*
  • Hyperlipoproteinemia Type IV / metabolism
  • Isoelectric Focusing
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Phenotype
  • Receptors, Cell Surface / analysis


  • Apolipoproteins E
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Receptors, Cell Surface

Associated data

  • GENBANK/K00396
  • GENBANK/X00199