title: Fetal Val108/158Met catechol-O-methyltransferase (COMT) polymorphism and placental COMT activity are associated with the development of preeclampsia.
abstract: OBJECTIVE
  To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels.
  
  
  METHODS
  Prospective case-control study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  A total of 53 preeclamptic and 72 normal pregnant women.
  
  
  METHODS
  Maternal and cord blood samples and placental tissue samples were obtained.
  
  
  METHODS
  Maternal and fetal COMT and MTHFR polymorphisms were genotyped. Maternal plasma 2-ME and homocysteine levels, and expression and activity of placental COMT were measured.
  
  
  RESULTS
  The odds ratio for the risk of preeclampsia for fetal COMT Met/Met was 3.22, and it increased to 8.65 when associated with fetal MTHFR TT. Placental COMT activity and expression were influenced by genotype, but COMT activity in preeclamptic placentas did not differ from control pregnancies. There was no association between any genotypes and maternal 2-ME. Homocysteine levels were higher in women with preeclampsia than in normal pregnancies, and were inversely correlated with 2-ME plasma levels, indicating that its altered metabolism may lower COMT activity in vivo.
  
  
  CONCLUSIONS
  Fetal Met-Met COMT genotype reduces COMT placental expression and activity in vitro and increases preeclampsia, risk but it does not explain the difference in maternal 2-ME levels between preeclamptic and normal pregnancies. However, the preeclamptic patients had elevated homocysteine levels that correlated inversely with 2-ME, indicating that an altered methionine-homocysteine metabolism may contribute to reduce COMT activity in vivo and explain the decreased levels of 2-ME in preeclamptic women.
authors.affiliation: Department of Gynecology and Obstetrics, "Virgen de la Arrixaca" Clinical University Hospital, El Palmar, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Pertegal
authors.affiliation: Department of Physiology, School of Medicine, University of Murcia, IMIB-Arrixaca, Espinardo, Spain. Electronic address: fjfenoy@um.es.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Fenoy
authors.affiliation: Department of Physiology, School of Medicine, University of Murcia, IMIB-Arrixaca, Espinardo, Spain.
authors.forename: Moisés
authors.initials: M
authors.lastname: Hernández
authors.affiliation: Division of Preventive Medicine and Public Health, Department of Health and Social Sciences, School of Medicine, University of Murcia, IMIB-Arrixaca, Espinardo, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Mendiola
authors.affiliation: Department of Gynecology and Obstetrics, "Virgen de la Arrixaca" Clinical University Hospital, El Palmar, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Delgado
authors.affiliation: Department of Physiology, School of Medicine, University of Murcia, IMIB-Arrixaca, Espinardo, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Bonacasa
authors.affiliation: Análisis Genéticos Ancor, Alicante, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Corno
authors.affiliation: Department of Physiology, School of Medicine, University of Murcia, IMIB-Arrixaca, Espinardo, Spain.
authors.forename: Bernardo
authors.initials: B
authors.lastname: López
authors.affiliation: Department of Pediatrics, "Virgen de la Arrixaca" Clinical University Hospital, El Palmar, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Bosch
authors.affiliation: Department of Physiology, School of Medicine, University of Murcia, IMIB-Arrixaca, Espinardo, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
mesh_terms: D000077584:2-Methoxyestradiol; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000097:blood / Q000235:genetics*; D016009:Chi-Square Distribution; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000201:enzymology; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006710:Homocysteine / Q000097:blood; D006785:Hospitals, University; D006801:Humans; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D010920:Placenta / Q000201:enzymology; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D011247:Pregnancy; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D004958:Estradiol; D000077584:2-Methoxyestradiol; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: 2-Methoxyestradiol; COMT; MTHFR; genotype; preeclampsia