Identification of Human Apolipoprotein E Variant Gene: Apolipoprotein E7 (GIu_{244, 245}→Lys_{244, 245})

Abstract

Apolipoprotein E (apoE) is one of the protein moieties of the human serum lipoproteins. Three major isoforms of apoE (apoE2, apoE3, and apoE4) and minor variant isoforms (apoEl, apoE5, and apoE7) have been detected by isoelectric focusing. In this study we have cloned the apoE7 gene from a patient with the apoE3/E7 phenotype associated with hypertriglyceridemia and diabetes mellitus. DNA sequencing revealed that the apoE7 gene has two base substitutions (G →A) changing GIu_{244, 245}→Lys_{244, 245}, compared with the apoE3 gene. The replacement of the two amino acids is consistent with the result of isoelectric focusing of the apoE7 isoprotein, which shifts to four positively charged units compared with the apoE3 isoprotein.