title: The PAI-1 4G/5G polymorphism is not associated with an increased risk of adverse pregnancy outcome in asymptomatic nulliparous women.
abstract: BACKGROUND
  Plasminogen activator inhibitor type 1 (PAI-1) is an important regulator of fibrinolysis. A common deletion polymorphism that results in a sequence of 4G instead of 5G in the promoter region of the gene is associated with a small increase in the risk of venous thromboembolism. Its potential association with adverse pregnancy events remains controversial.
  
  
  OBJECTIVE
  We aimed to assess the impact of the 4G PAI-1 polymorphism on pregnancy outcomes in women who had no prior history of adverse pregnancy outcomes or personal or family history of venous thromboembolism.
  
  
  METHODS
  This study represents a secondary investigation of a prior prospective cohort study investigating the association between inherited thrombophilias and adverse pregnancy events in Australian women. Healthy nulliparous women were recruited to this study prior to 22 weeks gestation. Genotyping for the 4G/5G PAI-1 gene was performed using Taqman assays in an ABI prism 7700 Sequencer several years after the pregnancy was completed. Pregnancy outcome data were extracted from the medical record. The primary outcome was a composite comprising development of severe pre-eclampsia, fetal growth restriction, major placental abruption, stillbirth or neonatal death.
  
  
  RESULTS
  Pregnancy outcome data were available in 1733 women who were successfully genotyped for this polymorphism. The primary composite outcome was experienced by 139 women (8% of the cohort). Four hundred and fifty-nine women (26.5%) were homozygous for the 4G deletion polymorphism, while 890 (51.4%) were heterozygous. Neither homozygosity nor heterozygosity for the PAI-1 4G polymorphism was associated with the primary composite outcome (homozygous OR = 1.30, 95% CI = 0.81-2.09, P = 0.28, heterozygous OR = 0.84, 95% CI = 0.53-1.31, P = 0.44) or with the individual pregnancy complications.
  
  
  CONCLUSIONS
  The PAI-1 4G polymorphism is not associated with an increase in the risk of serious adverse pregnancy events in asymptomatic nulliparous women.
authors.affiliation: Department of Perinatal Medicine, The Royal Women's Hospital, Parkville, Australia. jo.said@thewomens.org.au
authors.forename: J M
authors.initials: JM
authors.lastname: Said
authors.forename: R
authors.initials: R
authors.lastname: Tsui
authors.forename: A J
authors.initials: AJ
authors.lastname: Borg
authors.forename: J R
authors.initials: JR
authors.lastname: Higgins
authors.forename: E K
authors.initials: EK
authors.lastname: Moses
authors.forename: S P
authors.initials: SP
authors.lastname: Walker
authors.forename: P T
authors.initials: PT
authors.lastname: Monagle
authors.forename: S P
authors.initials: SP
authors.lastname: Brennecke
mesh_terms: D000037:Abruptio Placentae / Q000097:blood / Q000235:genetics; D000328:Adult; D058070:Asymptomatic Diseases; D005260:Female; D005313:Fetal Death / Q000097:blood / Q000235:genetics; D005317:Fetal Growth Retardation / Q000097:blood / Q000235:genetics; D005342:Fibrinolysis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D010298:Parity; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000235:genetics*; D011256:Pregnancy Outcome; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D050497:Stillbirth / Q000235:genetics; D014739:Victoria
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human