Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women.

Abstract:

OBJECTIVE:Postmenopausal estradiol (E(2)) levels vary widely between individuals and this variation is an important determinant of diseases such as osteoporosis. It has been suggested that the estrogen receptor alpha (ESR1) gene may influence peripheral E(2) levels, but the role of common sequence variations in the ESR1 gene is unclear. METHODS:In 631 postmenopausal women and 528 men from the Rotterdam Study, a population-based, prospective cohort study of individuals aged 55 years and over, ESR1 PvuII-XbaI haplotypes were determined and correlated with plasma E2 levels. RESULTS:In women, haplotype 1 (T-A) was significantly associated with an allele-dose-dependent decrease in E(2). After adjusting for age, body mass index, years since menopause and testosterone levels, plasma E(2) levels decreased by 1.90 pmol/l per allele copy of this haplotype (P < 0.05). Extreme genotypes, representing 23 and 27% of the population, varied by 3.93 pmol/l. No association with plasma testosterone was observed. In a subset of 446 women, no association of genotype with plasma concentrations of dehydroepiandrosterone sulfate, androstenedione or estrone was seen. In men, none of the sex hormone levels was associated with the ESR1 PvuII-XbaI haplotypes. CONCLUSION:We have demonstrated a role for genetic variations in the ESR1 gene in determining post-menopausal E(2) levels in women.

journal_name

Eur J Endocrinol

authors

Schuit SC,de Jong FH,Stolk L,Koek WN,van Meurs JB,Schoofs MW,Zillikens MC,Hofman A,van Leeuwen JP,Pols HA,Uitterlinden AG

doi

10.1530/eje.1.01973

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

327-34

issue

2

eissn

0804-4643

issn

1479-683X

pii

153/2/327

journal_volume

153

pub_type

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