Apolipoprotein (apo) E mediates the removal of chylomicron and very low density 
lipoprotein remnants from plasma. It is polymorphic in sequence and the products 
of the three common alleles (epsilon 2, epsilon 3, epsilon 4) differ from one 
another in their binding to lipoprotein receptors. ApoE2 is defective in binding 
and homozygosity for apoE2 is associated with type III hyperlipoproteinemia 
(HLP). Other rare isoforms of apoE have been found to be associated either with 
dominant type III HLP or with the development of hypertriglyceridemia. We 
identified a 42 year-old hypertriglyceridemic woman with an apoE phenotype 3/1. 
Restriction isotyping using AflIII/HaeII resulted in an apparent apoE genotype 
3/2, suggesting that the mutation occurred in an epsilon 2 allele. DNA sequence 
analysis revealed a C-->T point mutation at the first position of the codon for 
amino acid residue 180 of the mature apoE. This predicted a change 
Arg(180)-->Cys. The mutation altered a recognition site for the endonuclease 
HaeII, which allowed us rapidly to screen for this mutation. In relatives of the 
proband, apoE1 Baden was consistently associated with hypertriglyceridemia. 
Similar to other apoE variants linked to hypertriglyceridemia, the 
Arg(180)-->Cys mutation is located within the lipid binding domain of apoE. We 
therefore suggest that apoE1 Baden may cause hypertrigylceridemia, possibly by 
inhibiting the hydrolysis of triglycerides associated with very low density 
lipoproteins.