Genetic variation in human apolipoprotein E.

Genetic variation in human apoprotein E was studied using the technique of isoelectric focusing applied to delipidated very low density lipoprotein from 426 Christchurch blood donors and 7 patients with type III hyperlipoproteinemia. Six phenotypes were distinguishable by the relative proportions of the apoprotein E isomers. In the blood donors, observed frequencies for these were: E3/3 = 51.4%; E4/3 = 25.0%; E4/4 = 1.0%; E3/2 - 20.0%; E4/2 = 1.2%; and E2/2 = 1.4%. All seven patients with type III hyperlipoproteinemia exhibited phenotype E2/2. Family studies of apoprotein E variants support a mode of inheritance controlled by three alleles acting at one gene locus. On this basis, the alleles occurred in the blood donor population with frequencies of 0.72 for the epsilon 3 allele, 0.12 for the epsilon 2 allele, and 0.16 for the epsilon 4 allele. The epsilon 2 allele influenced plasma cholesterol. The mean plasma cholesterol in subjects heterozygous for the epsilon 2 allele was 5.32 mmol/l, very significantly less (P less than 0.01) than the mean of 5.84 mmol/l in an age- and sex-matched group of subjects without this allele in their genotype. The mean plasma cholesterol value of 4.92 mmol/l for the five individuals homozygous for the epsilon 2 allele was also significantly less (P less than 0.05) than for age- and sex-matched subjects without the epsilon allele, whose mean was 5.80 mmol/l.