Increased Frequency of Apolipoprotein ∈₄ Allele in Type II Diabetes With Hypercholesterolemia

The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulindependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type lib hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, apoE4/4, and apoE4/2) were highest in the type IIa group (51.4%), followed by the type Mb group (38.1%) and the normolipidemic group (16.4%), respectively, whereas the frequency of the most common phenotype, apoE3/3, was lowest in the type IIa group (48.6%), followed by the type lib group (61.9%) and the normolipidemic group (79.9%), respectively. There were significant differences in the apoE phenotype frequencies between the normolipidemic group and the type IIa and Mb groups. The frequency of the ∈₄ allele was significantly higher in the type IIa (28.6%) and Mb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the ∈₃ allele was significantly lower in the type IIa (71.4%) and Mb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the ∈₂ allele tended to be lower in diabetic patients with hypercholesterolemia. In addition, these frequencies were also examined in nondiabetic subjects (n = 59). The frequency of the ∈₄ allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemicnondiabetic subjects (15.3%). These data suggest that diabetic patients with the ∈₄ allele may be more susceptible to hypercholesterolemia than diabetic patients without the ∈₄ allele and possibly nondiabetic subjects with the ∈₄ allele, although the underlying mechanism is unknown.