Estrogen replacement therapy, serum lipids, and polymorphism of the apolipoprotein E gene

Background: Pharmacogenomics, the study of genetic loci that modulate drug responsiveness, may help to explain why estrogen replacement therapy (ERT) has differential effects on serum lipid and lipoprotein concentrations hn p ostmenopausal women who inherit distinct alleles of the apolipoprotein E ge ne (APOE). Methods: We compared total-cholesterol, triglyceride, and lipoprotein (LDL and HDL) concentrations in 66 postmenopausal women receiving ERT ([+]ERT) w ith 174 postmenopausal women not receiving ERT ([-]ERT), controlling for th ree APOE genotypes divided into three groups: E2 (epsilon 2/epsilon 3, n = 31), E3 (epsilon 3/epsilon 3, n = 160), and E4 (epsilon 3/epsilon 4 + epsil on 4/epsilon 4, n = 49). Results: Mean total-cholesterol concentrations were lower in all three [+]E RT groups compared with their [-]ERT counterparts but were statistically si gnificant only for women in group E4 (P = 0.014). The mean LDL-cholesterol concentrations were significantly lower in all three [+]ERT groups compared with their [-]ERT counterparts (P less than or equal to 0.005). Although a ll three groups of [+]ERT women fended to have higher mean HDL-cholesterol concentrations compared with their [-]ERT counterparts, the differences wer e not statistically significant. [+]ERT women in groups E2 and E3 had signi ficantly higher (P <0.05) triglyceride concentrations than their [-]ERT cou nterparts, In [+]ERT women, the ratios of total and LDL-cholesterol to HDL- cholesterol were significantly higher in group E3 and E4 women compared wit h E2 women (P<0.006). Group E4 [+]ERT women had ratios of total and LDL-cho lesterol to HDL-cholesterol that were comparable to group E2 [-]ERT women. Conclusions: Triglyceride concentrations in group E2 [+]ERT women may need to be monitored more closely than those in E3 or E4 [+]ERT women. Group E4 women should probably be targeted for ERT. Results suggest that APOE genoty pes have a differential effect on serum lipids and lipoproteins in [+]ERT p ostmenopausal women. (C) 1999 American Association for Clinical Chemistry.