HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Schuit, S. C E Articles by Uitterlinden, A. G Search for Related Content PubMed PubMed Citation Articles by Schuit, S. C E Articles by Uitterlinden, A. G

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

¹ Departments of Internal Medicine and ² Epidemiology and Biostatistics, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands

(Correspondence should be addressed to A G Uitterlinden; Email: a.g.uitterlinden{at}erasmusmc.n)

Objective: Postmenopausal estradiol (E₂) 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 E₂ 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 E₂. After adjusting for age, body mass index, years since menopause and testosterone levels, plasma E₂ 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 E₂ levels in women.

This article has been cited by other articles:

				L. Stolk, J. B. J. van Meurs, M. Jhamai, P. P. Arp, J. P. T. van Leeuwen, A. Hofman, F. H. de Jong, H. A. P. Pols, and A. G. Uitterlinden The Catechol-O-Methyltransferase Met158 Low-Activity Allele and Association with Nonvertebral Fracture Risk in Elderly Men J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3206 - 3212. [Abstract] [Full Text] [PDF]

				S. Altmae, K. Haller, M. Peters, O. Hovatta, A. Stavreus-Evers, H. Karro, A. Metspalu, and A. Salumets Allelic estrogen receptor 1 (ESR1) gene variants predict the outcome of ovarian stimulation in in vitro fertilization Mol. Hum. Reprod., August 1, 2007; 13(8): 521 - 526. [Abstract] [Full Text] [PDF]

				E. Murphy and C. Steenbergen Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury Cardiovasc Res, August 1, 2007; 75(3): 478 - 486. [Abstract] [Full Text] [PDF]

				S. S. Boekhoorn, J. R. Vingerling, A. G. Uitterlinden, J. B. J. Van Meurs, C. M. van Duijn, H. A. P. Pols, A. Hofman, and P. T. V. M. de Jong Estrogen Receptor {alpha} Gene Polymorphisms Associated with Incident Aging Macula Disorder Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1012 - 1017. [Abstract] [Full Text] [PDF]

				Y.-Y. Hsieh, Y.-K. Wang, C.-C. Chang, and C.-S. Lin Estrogen receptor {alpha}-351 XbaIG and -397 PvuIIC-related genotypes and alleles are associated with higher susceptibilities of endometriosis and leiomyoma Mol. Hum. Reprod., February 1, 2007; 13(2): 117 - 122. [Abstract] [Full Text] [PDF]