title: ACE gene in pregnancy complications: Insights into future vascular risk.
abstract: OBJECTIVE
  A history of placenta-mediated pregnancy complications (PMPCs) increases the risk of cardiovascular disease later in life, possibly related to the persistence of endothelial dysfunction. We performed this study in order to search for a common genetic background shared by women with a history of PMPC and vascular disorders, due to their common pathophysiologic pathway of endothelial dysfunction.
  
  
  METHODS
  We analyzed the prevalence of seven polymorphisms in ACE, AGTR1, AGT, and eNOS genes, endothelial-function related, in 290 women with a history of premature cardiovascular events (CVDs), and in 367 women with a history of PMPC (preeclampsia (PE), stillbirth (SB), and small for gestational age (SGA)), compared with 300 healthy women (HW) who delivered after uneventful pregnancy (HW).
  
  
  RESULTS
  ACE D allele frequency was similar between women with history of CVD and PMPC, and significantly higher than that observed in HW [OR (95% CI) 1.91, p = 0.002, and OR (95% CI) 2.18, p < 0.0001, respectively]. In women carrying ACE-240T or eNOS-786C allele, a two-fold increase in SB susceptibility was evidenced (p = 0.004 and p = 0.005, respectively). Women with a history of SB and premature CVD exhibited a significantly higher unfavorable allelic burden ≥ 3 in comparison to that observed in HW (p < 0.0001 and p = 0.002, respectively).
  
  
  CONCLUSIONS
  Our findings demonstrate a common genetic background shared by women with a history of vascular disorders and PMPCs; pregnancy may be considered a window to future cardiovascular risk; therefore, "non-classic" genetic biomarkers of endothelial dysfunction might allow one to identify women who could have a greater benefit for an early cardiovascular screening and prevention.
authors.affiliation: a Department of Experimental and Clinical Medicine , University of Florence, Thrombosis Centre, Largo Brambilla , Florence , Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.affiliation: a Department of Experimental and Clinical Medicine , University of Florence, Thrombosis Centre, Largo Brambilla , Florence , Italy.|b Fiorgen Foundation, Sesto F.no , Florence , Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Romagnuolo
authors.affiliation: a Department of Experimental and Clinical Medicine , University of Florence, Thrombosis Centre, Largo Brambilla , Florence , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.affiliation: a Department of Experimental and Clinical Medicine , University of Florence, Thrombosis Centre, Largo Brambilla , Florence , Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Rossi
authors.affiliation: c Department of Heart and Vessels , Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla , Florence , Italy.
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Cellai
authors.affiliation: c Department of Heart and Vessels , Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla , Florence , Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Rogolino
authors.affiliation: a Department of Experimental and Clinical Medicine , University of Florence, Thrombosis Centre, Largo Brambilla , Florence , Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
mesh_terms: D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007236:Infant, Small for Gestational Age; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012307:Risk Factors; D050497:Stillbirth / Q000235:genetics*
chemical_list: C534931:AGT protein, human; C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D052250:Nitric Oxide Synthase Type III; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Cardiovascular disease; nitric oxide synthase polymorphisms; placenta-mediated pregnancy complications; renin angiotensin system polymorphisms