ESR1 and APOE gene polymorphisms, serum lipids, and hormonal replacement therapy.

OBJECTIVES

The risks and benefits of hormone replacement therapy (HRT) are, at least in part, mediated by the metabolic individuality of women. Therefore, we investigated the association between polymorphisms at the estrogen receptor 1 gene (ESR1) and at the apolipoprotein E gene (APOE) with lipid and lipoprotein levels in order to verify whether these concentrations are modulated by these gene variants in women with different hormonal status.

METHODS

One hundred and eighteen postmenopausal women using oral HRT with estrogen or estrogen plus progestagen (HRT+, mean age=56+/-6.7 years, 39-75 years) and 167 postmenopausal women that were not on HRT (HRT-, mean age=58+/-9.8 years, 38-85 years) participated in the study. The polymorphisms were genotyped by PCR-RFLP methods.

RESULTS

No significant effect of ESR1 genotypes or haplotypes and ESR1HRT interactions were detected on lipid levels in two-way analysis of variance. Postmenopausal women HRT nonusers carriers of the APOE4 allele had higher T-chol and LDL-C levels than postmenopausal women HRT nonusers carriers of the APOE3 and APOE2 allele. T-chol and LDL-C concentrations in postmenopausal users of HRT that were APOE4 carriers were similar to those in postmenopausal women nonusers of HRT homozygotes for APOE3 and APOE2 carriers. A significant APOE4/HRT interaction was detected on T-chol and LDL-C levels by multiple regression analysis.

CONCLUSION

The results from this study suggest that the HRT influence on T-chol and LDL-C levels is modulated by APOE isoforms but not by ESR1 polymorphisms.