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Hum. Reprod. Advance Access published online on November 11, 2004
Human Reproduction, doi:10.1093/humrep/deh600
© 2004 by European Society of Human Reproduction and Embryology
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Received March 25, 2004
Revised April 27, 2004
Accepted October 15, 2004

Article

No association of estrogen receptor {alpha} and cytochrome P450c17{alpha} polymorphisms with age at menopause in a Dutch cohort

Helen S. Kok 1, N. Charlotte Onland-Moret 2, Kristel M. van Asselt 1, Carla H. van Gils 2, Yvonne T. van der Schouw 2*, Diederick E. Grobbee 2, and Petra H.M. Peeters 2

1 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands; Department of Medical Genetics, University Medical Center Utrecht, The Netherlands; Department of Reproductive Medicine, University Medical Center Utrecht, The Netherlands
2 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands

* To whom correspondence should be addressed.
Yvonne T. van der Schouw, E-mail: Y.T.vanderSchouw{at}umcutrecht.nl


  Abstract

BACKGROUND: Age at menopause is under strong genetic control. So far, genetic variations of only one gene, the PvuII polymorphism of the estrogen receptor {alpha} (ER{alpha}) gene, have been shown to be associated with age at onset of menopause. This study aims to investigate whether PvuII, XbaI and B-variant polymorphisms of the ER{alpha} gene, and the MspAI polymorphism of the cytochrome P450c17{alpha} (CYP17) gene are associated with age at menopause in a Dutch cohort. METHODS: DNA was isolated from urine samples of 385 Caucasian women with natural menopause and the genotypes of the four polymorphisms were determined. A questionnaire was used for background characteristics. The genotypes of PvuII, XbaI, MspAI were obtained by PCR restriction fragment length polymorphism analysis. The B-variant was determined with an allele-specific oligonucleotide hybridization method. Two-sided t-tests were performed to assess the association between the four polymorphisms and menopausal age. The PvuII and XbaI polymorphisms were analysed separately as well as in a combined score. RESULTS: The results show that none of the polymorphisms independently, nor the combined genotypes for PvuII and XbaI, were associated with age at natural menopause. CONCLUSION: No evidence was found for a relationship between common variants of the ER{alpha} gene and the CYP17 gene with age at natural menopause.

Keywords: age at menopause; association study; cytochrome P450c17{alpha}; estrogen receptor a; polymorphism.
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