In this study, we present clinical feature of a novel case with homozygous
apolipoprotein (
apo) E5. The patient was a 53-year-old Japanese woman. She was from a small island off the coast of Kagoshima Prefecture, Japan. Her parents were first degree cousins. No corneal opacification,
xanthomatosis,
lymphadenopathy, or hepatosplenomegaly was observed. There have been no signs of clinically overt
atherosclerosis to date. Her serum total
cholesterol,
triglycerides (TG) and
high-density lipoprotein (
HDL)-cholesterol levels were 11.6, 6.1 and 1.2 mmol/l, respectively, and
apo A-I, A-II, B, C-II, C-III and E levels were 121, 34.8, 269, 10.4, 25.7 and 10.3 mg/dl, respectively. Serum
lipoprotein profile analyzed by
agarose gel electrophoresis and differential staining revealed markedly increased
cholesterol and TG in both beta and prebeta-migrated
lipoproteins, whereas alpha-migrated
lipoprotein showed decreased
cholesterol. Her
apo E isoform analyzed by isoelectric focusing (IEF) was found to be homozygous
apo E5. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis of her
apo E and
lipoprotein lipase (LPL) genes revealed that she had a homozygous
apo E (Glu3-->Lys) and heterozygous LPL variant Ser447 to Ter. Her son and daughter, both of whom had
hyperlipidemia, were found to have
apo E3/5 phenotype. Direct sequencing analysis of her
apo E gene confirmed a homozygous one
nucleotide change: G to A at
nucleotide position of 2836 in the exon 3, resulting in Glu3-->Lys mutation. This is the first report of
lipids and
lipoprotein profiles in patients with homozygous
apo E5 (Glu3-->Lys).