Journal of Lipid Research, Vol 31, 1005-1013, Copyright © 1990 by Lipid Research, Inc.
Normolipemic dysbetalipoproteinemia and hyperlipoproteinemia type III in subjects homozygous for a rare genetic apolipoprotein E variant (apoE1)
A Steinmetz, N Assefbarkhi, C Eltze, K Ehlenz, H Funke, A Pies, G Assmann and H Kaffarnik
Zentrum Innere Medizin, Endokrinologie, und Stoffwechsel, Universitat Marburg, FRG.
A family with three heterozygote and two homozygote carriers of the rare
apolipoprotein E1 isoform was detected by isoelectric focusing. One of the
homozygous patients had type III hyperlipidemia, while the other showed
normolipemic dysbetalipoproteinemia. Restriction fragment length analysis
as well as allele specific oligonucleotides were used to identify the
structural alterations forming the abnormal epsilon 1 genotype. Comparison
with the most common epsilon 3 allele showed that two base exchanges A for
G in codon 127 and T for G in codon 158 (Asp for Gly and Cys for Arg,
respectively) are responsible for the amino acid substitution which causes
the charge shift observed in isoelectric focusing. The same defects have
been described in the only previously characterized apoE1 (Weisgraber et
al. 1984. J. Clin. Invest. 73: 1024- 1033). In addition to the study by
Weisgraber and coworkers, who reported on a heterozygous patient, we here
describe the metabolic and clinical consequences of a homozygosity for this
rare allele. Changes in lipoprotein metabolism, as well as in clinical
phenotypes, were exactly identical to those seen in patients homozygous for
the epsilon 2 allele, which has in common with the epsilon 1 allele the
mutation in codon 158, but lacks the substitution in codon 127. In
addition, lipoprotein profiles of the epsilon 3/epsilon 1 heterozygotes
were indistinguishable from those of epsilon 3/epsilon 2 heterozygotes.
Therefore, we conclude that the additional mutation in codon 127 that
characterizes the epsilon 1 allele is of no functional importance in vivo.
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