it M/inchen Summary. Serum lipid concentrations of patients with familial defective apolipoprotein B-100 (FDB) show a high interindividual variability although the underlying defect is caused by a single point mutation. On the other hand, several genetic factors modulating serum cholesterol levels are known, such as DNA polymorphisms of the apopolipoprotein B or the apolipoprotein E (apo E) gene. To assess the effect of the apo E polymorphism on serum cholesterol, lipid levels of FDB patients (n= 36) were compared with those of a normolipidemic control group (n = 272) according to their apo E genotype. For the FDB group mean values of low-density lipoprotein (LDL) cholesterol (mg/dl) were 225.7 _+ 53.7 for E3/2 genotype (n = 3), 234.2+48.3 for E3/3 genotype (n=20), and 252.4_+73.8 for E4/3 genotype (n=13). Means of triglycerides (mg/dl) were 121.0_+21.2, 114.8_ 60.7, and 110.0+62.8 for the respective apo E genotypes. The calculated average effect of the apo E alleles on LDL cholesterol levels was -6 . 0 % for allele e2 and + 3.7% for e4 relative to the whole FDB group. The effect on triglyceride levels was +7.5% for e2 and -3 . 6 % for e4. The control group showed a similar variation in LDL cholesterol depending on the different apo E genotypes. About 6% of the total variation in LDL cholesterol can be accounted for by the apo E locus in normolipidemic and hypercholesterolemic individuals alike.