Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia

The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulin-dependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type IIb 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 IIb 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 IIb 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 IIb groups. The frequency of the epsilon 4 allele was significantly higher in the type IIa (28.6%) and IIb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type IIa (71.4%) and IIb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the epsilon 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 epsilon 4 allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemic nondiabetic subjects (15.3%). These data suggest that diabetic patients with the epsilon 4 allele may be more susceptible to hypercholesterolemia than diabetic patients without the epsilon 4 allele and possibly nondiabetic subjects with the epsilon 4 allele, although the underlying mechanism is unknown.