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Hum. Reprod. Advance Access published online on February 14, 2006
Human Reproduction, doi:10.1093/humrep/del015
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received October 12, 2005
Revised December 28, 2005
Accepted January 8, 2006

Article

Estrogen receptor 1 haplotype does not regulate oral contraceptive-induced changes in haemostasis and inflammation risk factors for venous and arterial thrombosis

Moniek P.M. de Maat 1 *, E.-M. Bladbjerg 2, C. Kluft 3, U.H. Winkler 4, H. Rekers 5, S.O. Skouby 6, and J. Jespersen 2

1 Department of Thrombosis Research, University of Southern Denmark and Department of Clinical Biochemistry, Ribe County Hospital, Esbjerg, Denmark; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
2 Department of Thrombosis Research, University of Southern Denmark and Department of Clinical Biochemistry, Ribe County Hospital, Esbjerg, Denmark
3 Department of Thrombosis Research, University of Southern Denmark and Department of Clinical Biochemistry, Ribe County Hospital, Esbjerg, Denmark; Department of Biomedical Research, TNO Prevention and Health, Leiden, The Netherlands
4 Klinikum Wetzlar-Braunfels, Wetzlar, Germany
5 Organon B.V., Oss, The Netherlands
6 Department of Obstetrics and Gynecology, Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark

* To whom correspondence should be addressed.
Moniek P.M. de Maat, E-mail: m.demaat{at}erasmusmc.nl


  Abstract

BACKGROUND: Administration of oral contraceptives (OCs) has profound effects on the plasma levels of haemostasis and inflammation variables, resulting in an increased thrombosis risk. Individuals show large differences in the response of these variables to OCs. Polymorphism in the estrogen receptor-1 (ER1) gene may explain part of this inter-individual response. METHODS: We investigated the relationship between variants (c.454-397T>C and c.454-351A>G polymorphisms and the combined haplotype) in the ER1 gene in relation to changes in haemostasis and inflammation variables that are known risk factors for thrombosis in 507 healthy, nonsmoking, nulliparous women receiving six cycles of monophasic OCs with 20, 30 or 50 µg/day estrogen. RESULTS: A significant relationship was observed between the ER1 haplotype and changes in tissue-type plasminogen activator activity (P = 0.006), but no clear interaction pattern between the genotypes or between the estrogen doses was seen. No relationships were observed for the other variables, neither in the haplotype nor in the single polymorphism analysis. CONCLUSION: The ER1 haplotype does not have a strong effect on the estrogen-induced changes in haemostasis and inflammation risk markers for arterial and venous thrombosis.

Keywords: estrogen receptor 1/haemostasis/inflammation/oral contraceptives/polymorphism.
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