Fetal Val108/158Met catechol-O-methyltransferase (COMT) polymorphism and placental COMT activity are associated with the development of preeclampsia

Fertil Steril. 2016 Jan;105(1):134-43.e1-3. doi: 10.1016/j.fertnstert.2015.09.019. Epub 2015 Oct 9.


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.

Design: Prospective case-control study.

Setting: University hospital.

Patient(s): A total of 53 preeclamptic and 72 normal pregnant women.

Intervention(s): Maternal and cord blood samples and placental tissue samples were obtained.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): 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.

Keywords: 2-Methoxyestradiol; COMT; MTHFR; genotype; preeclampsia.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Methoxyestradiol
  • Adult
  • Biomarkers / blood
  • Blood Pressure / genetics*
  • Case-Control Studies
  • Catechol O-Methyltransferase / blood
  • Catechol O-Methyltransferase / genetics*
  • Chi-Square Distribution
  • Estradiol / analogs & derivatives
  • Estradiol / blood
  • Female
  • Fetal Blood / enzymology
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Homocysteine / blood
  • Hospitals, University
  • Humans
  • Logistic Models
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Multivariate Analysis
  • Odds Ratio
  • Phenotype
  • Placenta / enzymology
  • Polymorphism, Single Nucleotide*
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / enzymology
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Spain


  • Biomarkers
  • Homocysteine
  • Estradiol
  • 2-Methoxyestradiol
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • COMT protein, human
  • Catechol O-Methyltransferase