title: 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 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.
authors.affiliation: Fetal Medicine Unit, Department of Obstetrics and Gynecology, Universidad de los Andes, San Carlos de Apoquindo, Santiago, Chile.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Pérez-Sepúlveda
authors.forename: María José
authors.initials: MJ
authors.lastname: Torres
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Valenzuela
authors.forename: Raimundo
authors.initials: R
authors.lastname: Larraín
authors.forename: Horacio
authors.initials: H
authors.lastname: Figueroa-Diesel
authors.forename: José
authors.initials: J
authors.lastname: Galaz
authors.forename: Jyh Kae
authors.initials: JK
authors.lastname: Nien
authors.forename: Ramón
authors.initials: R
authors.lastname: Serra
authors.forename: Luis
authors.initials: L
authors.lastname: Michea
authors.forename: Sebastián E
authors.initials: SE
authors.lastname: Illanes
mesh_terms: D000077584:2-Methoxyestradiol; D000328:Adult; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000097:blood* / Q000235:genetics; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011446:Prospective Studies; D050257:Tubulin Modulators / Q000097:blood*
chemical_list: D050257:Tubulin Modulators; D004958:Estradiol; D000077584:2-Methoxyestradiol; D002394:Catechol O-Methyltransferase