Apolipoprotein E genotype and response of lipid levels to postmenopausal estrogen use.

The allelic variation of Apolipoprotein E (ApoE) influences serum lipid levels. Postmenopausal estrogen replacement therapy (ERT) has favorable effects on the serum lipid profile. We examined the effect of ApoE genotype on lipid response to ERT in 692 community-dwelling women aged 60 and older. ApoE genotypes were categorized into three groups: ApoE 2 (E2/E2+E2/E3, n=94), ApoE 3 (E3/E3, n=430), and ApoE 4 (E3/E4+E4/E4, n=142). Compared to 497 women not using ERT, 169 women currently using ERT were younger (P=0.01), had lower levels of total cholesterol (TC; P=0.10) and low-density lipoprotein (P<0.001), higher levels of high-density lipoprotein (HDL; P<0.001) and triglycerides (TG; P=0.009), and were more likely to have had a surgical menopause (P<0.001). No significant differences in body mass index, alcohol intake, physical activity, or cigarette smoking were found between current ERT users and nonusers (P>0.10). There was a significant interaction between ApoE 2 and ERT for HDL levels: women with ApoE 2 using ERT had the highest HDL levels, and women with ApoE 2 not using ERT had the lowest HDL levels (P=0.015). The unfavorable effect of ApoE 4 genotype on lipoproteins is not altered by HRT, but ApoE 2 genotype modulates the HDL-ERT association in older women.