Analysis of Apolipoprotein E7 (Apolipoprotein E-Suita) Gene from a Patient with Hyperlipoproteinemia1

Abstract

We have isolated and analyzed apolipoprotein E7 gene from a patient with hyperlipoproteinemia. Apolipoprotein E7 (apolipoprotein E-Suita) is a variant of apolipoprotein E with four additional units of positive charge compared to apolipoprotein E3, which is the major isoform of apolipoprotein E. The heterozygous gene of apolipoprotein E7/3 from the patient was cloned into lambda phage. The cloned apolipoprotein E genes were subcloned into a murine retrovirus shuttle vector and were expressed. Two out of five clones expressed apolipoprotein E7. The analysis of the nucleotide sequence of the exon and exon-intron boundary regions has shown two G-to-A nucleotide substitutions in the 548 and 551 nucleotide positions from the 5'-end of the fourth exon. These two base substitutions change the amino acid residues -Glu-Glu- to -Lys-Lys- at the 244 and 245 positions from the amino-terminus of the mature protein, and give four additional units of positive charge to the molecule.