title: Association of fetal-derived hypermethylated RASSF1A concentration in placenta-mediated pregnancy complications.
abstract: OBJECTIVE
  To assess whether fetal-derived hypermethylated RASSF1A concentrations in maternal plasma during pregnancy are altered in pregnancies associated with placental dysfunction manifested by intrauterine growth restriction (IUGR), preeclampsia (PE), or placental previa (PP) and whether this alteration can be detected in susceptible subjects before the onset of clinical disease.
  
  
  METHODS
  We performed a real-time quantitative polymerase chain reaction to quantify RASSF1A concentrations before and after methylation-sensitive restriction digestion in maternal plasma at 7-41 gestational weeks of normal pregnancies (n = 161), IUGR (n = 43), PE (n = 22), PP (n = 14) and non-pregnant women (n = 20).
  
  
  RESULTS
  A positive correlation was observed between fetal-derived hypermethylated RASSF1A concentration and gestational age for all study groups (r = 0.624, p < 0.001 for IUGR; r = 0.381, p = 0.042 for PE; r = 0.697, p < 0.001 for PP; r = 0.560, p < 0.001 for controls). The concentration of hypermethylated RASSF1A was relatively high at 7-14 gestational weeks in all patient groups. Hypermethylated RASSF1A concentration at 15-28 weeks was significantly higher in patients who subsequently developed IUGR (p = 0.002), PE (p < 0.001) or PP (p < 0.001) than in controls.
  
  
  CONCLUSIONS
  We first demonstrated increased concentration of fetal-derived hypermethylated RASSF1A sequences according to advancing gestation and before the onset of the clinical manifestation of pregnancy complications secondary to placental dysfunction, such as IUGR, PE and PP. Hypermethylated RASSF1A in maternal plasma may be useful as a potential biomarker to detect placental-mediated pregnancy complications, regardless of fetal gender and polymorphism.
authors.affiliation: Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center, Seoul, Republic of Korea.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kim
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: S Y
authors.initials: SY
authors.lastname: Park
authors.forename: H K
authors.initials: HK
authors.lastname: Ahn
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
authors.forename: H M
authors.initials: HM
authors.lastname: Ryu
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009994:Osmolar Concentration; D010920:Placenta / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D010922:Placenta Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010923:Placenta Previa / Q000097:blood / Q000235:genetics / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000097:blood* / Q000235:genetics / Q000378:metabolism*
chemical_list: C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins