In the process of screening
apolipoprotein (
apo) E genotypes in a population of subjects with
lipid abnormalities, we have identified five subjects (one homozygote and four heterozygotes) with an abnormal 109 base pairs band following
apo E restriction isotyping of amplified
DNA with the
restriction endonuclease CfoI. The polymerase chain reaction (PCR) products were cloned and their sequencing revealed a C-->A substitution at the first
nucleotide of
codon 136. This mutation resulted in an amino acid substitution Arg to Ser, previously described as
apo E2 Christchurch. Family studies were carried out for four of the probands. In these kindreds, stepwise multiple regression analyses indicated that 78% of the
cholesterol variability in men was predicted by body mass index, age and the rare
apo E2 (Arg136-->Ser) variant. In women, age and the
apo E2 (Arg136-->Ser variant predicted 54.9% of the variability in
cholesterol levels. Linkage analysis suggested that the presence of the
apo E2 (Arg136-->Ser) variant was linked with the occurrence of
cholesterol enriched
triglyceride rich
lipoproteins and with an incomplete dominance of
type III hyperlipoproteinemia. Our data indicates that this mutation may be a relatively common cause of
dyslipidemia in the Spanish population.