Associations between apolipoprotein E genotype and circulating F2-isoprostane levels in humans

Apolipoprotein E (apoE), an important determinant of plasma lipoprotein metabolism, has three common alleles (ε2, ε3, and ε4). Population studies have shown that the risk of diseases characterized by oxidative damage, such as coronary heart disease and Alzheimer's disease, is significantly higher in ɛ4 carriers. We evaluated the association between apoE genotypes and plasma F2‐isoprostane levels, an index of lipid peroxidation, in humans. Two hundred seventy‐four healthy subjects (104 males, 170 females; 46.9±13.0 yr; 200 whites, 74 blacks; 81 nonsmokers, 64 passive smokers, and 129 active smokers) recruited for a randomized clinical antioxidant intervention trial were included in this analysis. ApoE genotype was determined by PCR and restriction enzyme digestion. Free plasma F2‐isoprostane was measured by GC‐MS. Genotype groups were compared using multiple regression analysis with adjustment for sex, age, race, smoking status, body mass index, plasma ascorbic acid, and β‐carotene. Subjects with ε3/ε4 and ε4/ε4 genotype (ε4‐carriers) and with ε2/ε3 and ε3/ε3 (non‐ε4‐carriers) were pooled for analysis. In subjects with high cholesterol levels (total cholesterol above 200 mg/dl), plasma F2‐isoprostane levels were 29% higher in ε4 carriers than in non‐ε4‐carriers (P=0.0056). High‐cholesterol subjects that are ε4 carriers have significantly higher levels of lipid peroxidation as assessed by circulating F2‐isoprostane levels.