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Clinical Chemistry 45: 1214-1223, 1999;
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(Clinical Chemistry. 1999;45:1214-1223.)
© 1999 American Association for Clinical Chemistry, Inc.

Articles

Estrogen Replacement Therapy, Serum Lipids, and Polymorphism of the Apolipoprotein E Gene

Philip J. Garry1,a, Richard N. Baumgartner2, Steven G. Brodie4, George D. Montoya3, Hwa Chi Liang3, Robert D. Lindeman2 and Thomas M. Williams1

Departments of
1 Pathology and
2 Medicine, and
3 Clinical Nutrition Program, University of New Mexico School of Medicine, Albuquerque, NM 87131.
4 Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
a Address correspondence to this author at: Department of Pathology, Room 215, Surge Bldg., University of New Mexico Health Sciences Center, 2701 Frontier Place NE, Albuquerque, NM 87131. Fax 505-272-9135; e-mail pgarry{at}salud.unm.edu

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 in postmenopausal women who inherit distinct alleles of the apolipoprotein E gene (APOE).

Methods: We compared total-cholesterol, triglyceride, and lipoprotein (LDL and HDL) concentrations in 66 postmenopausal women receiving ERT ([+]ERT) with 174 postmenopausal women not receiving ERT ([-]ERT), controlling for three 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 + {epsilon}4/{epsilon}4, n = 49).

Results: Mean total-cholesterol concentrations were lower in all three [+]ERT groups compared with their [-]ERT counterparts but were statistically significant 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 <=0.005). Although all three groups of [+]ERT women tended to have higher mean HDL-cholesterol concentrations compared with their [-]ERT counterparts, the differences were not statistically significant. [+]ERT women in groups E2 and E3 had significantly higher (P <0.05) triglyceride concentrations than their [-]ERT counterparts. In [+]ERT women, the ratios of total and LDL-cholesterol to HDL-cholesterol were significantly higher in group E3 and E4 women compared with E2 women (P <0.006). Group E4 [+]ERT women had ratios of total and LDL-cholesterol 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 genotypes have a differential effect on serum lipids and lipoproteins in [+]ERT postmenopausal women.© 1999 American Association for Clinical Chemistry




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