Are polymorphisms in oestrogen receptors genes associated with lipid levels in response to hormone therapy?
BACKGROUND
Polymorphisms in the oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) genes are associated with intermediate or endpoint markers of cardiovascular disease and with the efficacy of postmenopausal hormone therapy (HT). Contradictory findings have been described in the past and the role of these genetics variants remains unclear.


METHODS
A cross-sectional study was carried out with 266 postmenopausal women, of whom 115 received oral HT (HT+) and 151 did not receive any HT (HT-). We analysed three single-nucleotide polymorphisms (SNPs) in ESR1 (rs1801132, rs7757956 and rs2813544) and two in ESR2 (rs3020450 and rs7154455) and derived haplotypes with three additional polymorphisms that had been previously investigated by our group (ESR1 rs2234693 and ESR2 rs1256049 and rs4986938).


RESULTS
The ESR1 rs2813544 polymorphism was associated with low-density lipoprotein cholesterol (LDL-C) in HT+ postmenopausal women (p = 0.044; pC = 0.388), while one ESR2 gene haplotype was associated with total cholesterol (T-chol) (p = 0.015; pC = 0.090) and LDL-C in HT+ postmenopausal women (p = 0.021; pC = 0.126).


CONCLUSIONS
Our findings suggest that, in HT+ postmenopausal women, the rs2813544 polymorphism may influence LDL-C levels and, as previously described, ESR2 rs1256049 is associated with T-chol and LDL-C. No previous study has investigated the association of this SNP set with lipoprotein levels in women while taking into account the hormonal status of the patients.
Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre – UFCSPA, Porto Alegre, RS, Brazil.
Lisiane
L
Smiderle
Vanessa Suñé
VS
Mattevi
Márcia
M
Giovenardi
Maria Celeste Osório
MC
Wender
Mara Helena
MH
Hutz
Silvana
S
Almeida
D000328:Adult; D000368:Aged; D054316:Biomarkers, Pharmacological / Q000097:blood; D001938:Brazil / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D015203:Reproducibility of Results; D012307:Risk Factors
D054316:Biomarkers, Pharmacological; D008078:Cholesterol, LDL; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D002784:Cholesterol