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Familial dysbetalipoproteinemic subjects with the E3/E2 phenotype exhibit an E2 isoform with only one cysteine residue

Most familial dysbetalipoproteinemic patients are E2/E2 homozygotes for the apolipoprotein E (apoE) polymorphism, whereas patients with the E4/E2 or E3/E2 phenotype are very rare. Three out of 41 dysbetalipoproteinemic patients from our lipid clinic appeared to be E3/E2 heterozygotes. ApoE protein phenotyping and DNA oligonucleotide hybridization techniques showed that all three patients exhibit an uncommon E2 variant that contains only one cysteine residue. These results suggest that, in contrast to the by far most frequently occurring E2(Arg158→ Cys) allele, heterozygosity for this uncommon E2 allele may cause familial dysbet‐alipoproteinemia. Preliminary family studies suggest that this uncommon E2 allele cosegregates with familial dysbetalipoproteinemia.