Effects of apolipoprotein E genotype on dietary-induced changes in high-density lipoprotein cholesterol in obese postmenopausal women

Lipid responses to a dietary intervention are highly variable between individuals. Part of this variation may be accounted for by individual differences in lipid-regulating genes that interact with diet to induce changes in lipoprotein metabolism. This study determined whether apolipoprotein E (APOE) genotype affects lipid responses to a low-fat, low-cholesterol diet in obese, postmenopausal women. Body weight and lipoprotein lipid responses to a 10-week, dietary intervention (American Heart Association [AHA] Step I) were compared in 61 women with the APOE 2/3 and APOE 3/3 genotype (APOE4-) and 18 women with the APOE 3/4 genotype (APOE4+) of a similar age, body composition, and maximal aerobic capacity. Body weight decreased by 2% in both groups, but changes in body weight correlated only with changes in low-density lipoprotein-cholesterol (LDL-C) (r = .27, P < .05). The dietary intervention decreased total cholesterol and LDL-C to a similar degree in both genotype groups. However, APOE4- women decreased high-density lipoprotein-cholesterol (HDL-C) by 17% ± 11% and increased triglycerides by 20% ± 41% in response to the diet, while APOE4+ women had a smaller decrease in HDL-C (-8% ± 12%) and no change in plasma triglyceride. These group differences were significant for HDL-C (P < .01) and approached significance for triglycerides (P = .08). Moreover, APOE4- women decreased HDL₂-C by 32% ± 45%, while APOE4+ women increased HDL₂-C by 12% ± 62% (P < .01 between groups). It may be prudent to genotype older women before initiating low-fat diet therapy, as those with the APOE4 allele benefit the most, while the lipid profile could worsen in women without the APOE4 allele.