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

Prenat Diagn. 2012 Nov;32(11):1053-8. doi: 10.1002/pd.3954. Epub 2012 Aug 7.

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 high-performance 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%; χ(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Methoxyestradiol
  • Adult
  • Case-Control Studies
  • Catechol O-Methyltransferase / genetics
  • Estradiol / analogs & derivatives*
  • Estradiol / blood
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Polymorphism, Single Nucleotide
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / genetics
  • Pregnancy
  • Pregnancy Trimester, First / blood*
  • Prospective Studies
  • Tubulin Modulators / blood*

Substances

  • Tubulin Modulators
  • Estradiol
  • 2-Methoxyestradiol
  • Catechol O-Methyltransferase