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Hum. Reprod. Advance Access originally published online on February 14, 2006
Human Reproduction 2006 21(6):1473-1476; 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

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 Maat1,2,7, E.-M. Bladbjerg1, C. Kluft1,3, U.H. Winkler4, H. Rekers5, S.O. Skouby6 and J. Jespersen1

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

7 To whom correspondence should be addressed at: Department of Hematology, Room Ee13.93, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: m.demaat{at}erasmusmc.nl

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.

Key words: estrogen receptor 1/haemostasis/inflammation/oral contraceptives/polymorphism


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