Phenotype of apolipoprotein E influences the lipid metabolic response of postmenopausal women to hormone replacement therapy

Objectives: We investigated whether the phenotype of apolipoprotein E (apo E) would influence the response of postmenopausal Japanese women to hormone replacement therapy (HRT). Methods: We measured the plasma levels of lipoprotein and apolipoprotein in 242 postmenopausal women at baseline and again after 12 months of HRT. Patients were divided into three groups according to apo E phenotype: E2+ (E2/2 and E2/3, n=21), E3/3 (n=176), E4+ (E3/4 and E4/4, n=45). Results: We found that the E4+ group had the highest levels of total and low density lipoprotein (LDL) cholesterol and apolipoprotein B, being significantly higher than in the E2+ group at baseline. The plasma levels of total and LDL cholesterol showed a significant decrease only in the E2+ and E3/3 groups after 12 months of HRT (E2+ group, total cholesterol −8.9% and LDL cholesterol −21.5%; E3/3 group, total cholesterol −2.9% and LDL cholesterol −9.5%). No significant difference in the reduction of total and LDL cholesterol was found in the E4+ group. Other lipid parameters did not differ in the three groups. Conclusions: These data show that the apo E phenotype influenced the response of lipid metabolism in postmenopausal women to HRT, especially in the reduction of LDL cholesterol. Therefore, apo E phenotyping may be important in predicting the cholesterol-lowering effect of HRT.