ESR1 and APOE gene polymorphisms, serum lipids, and hormonal replacement therapy.
OBJECTIVE
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 ESR1*HRT interactions were detected on lipid levels in two-way analysis of variance. Postmenopausal women HRT nonusers carriers of the APOE*4 allele had higher T-chol and LDL-C levels than postmenopausal women HRT nonusers carriers of the APOE*3 and APOE*2 allele. T-chol and LDL-C concentrations in postmenopausal users of HRT that were APOE*4 carriers were similar to those in postmenopausal women nonusers of HRT homozygotes for APOE*3 and APOE*2 carriers. A significant APOE*4/HRT interaction was detected on T-chol and LDL-C levels by multiple regression analysis.


CONCLUSIONS
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.
Almeida
Silvana
S
Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, and Departamento de Ginecologia e Obstetrícia, Hospital de Clínicas de Porto Alegre, RS, Brazil.
Fiegenbaum
Marilu
M
de Andrade
Fabiana M
FM
Osório-Wender
Maria C
MC
Hutz
Mara H
MH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017698:Postmenopause / Q000097:blood* / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D047628:Estrogen Receptor alpha; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol