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 HDL(2)-C by 32% +/- 45%, while APOE4+ women increased HDL(2)-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. Copyright 2002, Elsevier Science (USA). All rights reserved.