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


CONCLUSIONS
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.
de Maat
Moniek P M
MP
Department of Thrombosis Research, University of Southern Denmark and Ribe County Hospital, Esbjerg, Denmark. m.demaat@erasmusmc.nl
Bladbjerg
E-M
EM
Kluft
C
C
Winkler
U H
UH
Rekers
H
H
Skouby
S O
SO
Jespersen
J
J
D000328:Adult; D001158:Arteries / Q000473:pathology*; D003276:Contraceptives, Oral / Q000009:adverse effects*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006487:Hemostasis; D006801:Humans; D007249:Inflammation; D010960:Plasminogen Activators / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D020246:Venous Thrombosis / Q000139:chemically induced / Q000235:genetics*
D003276:Contraceptives, Oral; D047628:Estrogen Receptor alpha; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator