Low 2-methoxyestradiol levels at the first trimester of pregnancy are associated with the development of pre-eclampsia

Abstract

Objective To determine whether maternal plasma levels of 2-methoxyestradiol (2-ME) are decreased early in pregnancies that subsequently develop pre-eclampsia (PE) and whether this difference could be attributed to the presence of Val158Met catechol-O-methyltransferase (COMT) polymorphism in the placenta. Methods Clinical characteristics and plasma samples were collected at 11 to 14 weeks prospectively in a cohort of patients. From them, 13 PE and 72 control pregnant women were chosen. Plasma soluble fms-like tyrosine kinase1 and placental growth factor levels were measured by electrochemiluminescence and 2-ME was measured by highperformance liquid chromatography with mass spectrometry/mass spectrometry detection. At delivery, placental tissue was collected and the Val158Met COMT polymorphism was determined by restriction fragment length polymorphism–PCR. Results At 11 to 14 weeks, patients who would develop PE have significantly lower plasma levels of 2-ME than controls [1.9 2 standard error of the mean (SEM) vs 61.7 27 pg/mL, P<0.05]. The Val158Met polymorphism was more frequent in controls than in PE patients and the placental presence of COMT polymorphism was associated with a decreased risk of developing PE [PE: 23.1% vs control: 66.6%; w 2 = 10.9, p = 0.0041]. Conclusions Lower plasma concentrations of 2-ME during early pregnancy in patients who subsequently develop PE were found. Presence of placental Val158Met COMT polymorphism is associated with a decreased risk to develop PE, suggesting a protective role against PE.