雌激素替代疗法、血脂与载脂蛋白E基因多态性

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

作者信息

Garry P J, Baumgartner R N, Brodie S G, Montoya G D, Liang H C, Lindeman R D, Williams T M

机构信息

Departments of Pathology and Medicine, and Clinical Nutrition Program, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.

出版信息

Clin Chem. 1999 Aug;45(8 Pt 1):1214-23.

PMID:10430787

Abstract

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 (epsilon2/epsilon3, n = 31), E3 (epsilon3/epsilon3, n = 160), and E4 (epsilon3/epsilon4 + epsilon4/epsilon4, 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.

摘要

背景

药物基因组学是研究调节药物反应性的基因位点，它可能有助于解释为什么雌激素替代疗法（ERT）对携带不同载脂蛋白E基因（APOE）等位基因的绝经后女性的血清脂质和脂蛋白浓度有不同影响。

方法

我们比较了66名接受ERT（[+]ERT）的绝经后女性与174名未接受ERT（[-]ERT）的绝经后女性的总胆固醇、甘油三酯和脂蛋白（低密度脂蛋白和高密度脂蛋白）浓度，并将三种APOE基因型分为三组：E2（ε2/ε3，n = 31）、E3（ε3/ε3，n = 160）和E4（ε3/ε4 + ε4/ε4，n = 49）。

结果

所有三个[+]ERT组的平均总胆固醇浓度均低于其对应的[-]ERT组，但仅E4组女性具有统计学意义（P = 0.014）。所有三个[+]ERT组的平均低密度脂蛋白胆固醇浓度均显著低于其对应的[-]ERT组（P≤0.005）。尽管所有三组[+]ERT女性的平均高密度脂蛋白胆固醇浓度与其对应的[-]ERT组相比往往更高，但差异无统计学意义。E2组和E3组的[+]ERT女性的甘油三酯浓度显著高于其对应的[-]ERT组（P <0.05）。在[+]ERT女性中，E3组和E4组女性的总胆固醇和低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值显著高于E2组女性（P <0.006）。E4组[+]ERT女性的总胆固醇和低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值与E2组[-]ERT女性相当。