Apolipoprotein E phenotypes and plasma lipids in diabetic children and adolescents

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Abstract
Apolipoprotein E (apoE) polymorphism is a genetic determinant of serum lipoprotein levels and coronary heart disease risk. ApoE appears in three major isoforms E2, E3 and E4, coded by corresponding alleles ε2, ɛ3 and ɛ4. These give six different phenotypes. Patients with insulin dependent diabetes (IDDM) have been reported to have increased incidence of E2/2 homozygosity. We studied the frequencies of apoE phenotypes and their association with plasma lipids in 201 diabetic children, aged 2–17 years, and in 216 healthy controls with the same age range. Phenotyping was performed directly from plasma by iso-electric focusing and immunoblotting. Plasma total and high density lipoprotein (HDL) cholesterol (C) and triglycerides were determined by routine laboratory methods. Apolipoprotein A1 (apoA1) and B (apoB) were measured by turbidometry. There were no differences in apoE phenotype or allele distributions between the diabetic and control subjects. The frequencies of ɛ2, ɛ3, and ɛ4 in the diabetic and control children were 0.08 versus 0.07, 0.73 versus 0.72 and 0.19 versus 0.21. The difference in apoE2/2 frequencies (2.0 in diabetic and 0.5% in normal children) was not statistically significant. In the diabetic children, there was a distinct relation between apoE phenotype and plasma lipids; presence of apoE2 was associated with the lowest and that of apoE4 with the highest concentrations of total and low density lipoprotein (LDL) C, and apoB. Ratios of HDL-C/LDL-C and apoA1/apoB showed on opposite trend. The influence of apoE polymorphism on plasma lipids was less clear in the controls. ApoE polymorphism did not relate to body mass index, glycohaemoglobin A1c or daily insulin dosage. As compared to controls, diabetic children had significantly lower concentrations of total and LDL-C and apoB as well as higher ratios of HDL-C/LDL-C and apoA1/apoB. In conclusion, there was no difference in distribution of apoE phenotypes or alleles between diabetic and non-diabetic children. ApoE polymorphism proved to be an important genetic determinant of plasma lipid levels in patients with IDDM.