title: Genetic Contributions to the Development of Complications in Preterm Newborns.
abstract: OBJECTIVE
  We aimed to identify specific polymorphisms of genes encoding for vascular endothelial growth factor A (VEGFA), endothelial nitric oxide synthase (eNOS), renin-angiotensin system (angiotensinogen gene [AGT], angiotensinogen type 1 receptor [AGTR1], angiotensin-converting enzyme [ACE]), and heme oxygenase-1 (HMOX-1) in a cohort of preterm infants and correlate their presence with the development of respiratory distress syndrome (RDS) requiring mechanical ventilation (MV), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP).
  
  
  METHODS
  We carried out a retrospective study to evaluate the allele frequency and genotype distribution of polymorphisms of VEGFA, eNOS, AGT, AGTR1, ACE, and HMOX-1 in a population of preterm neonates (n=342) with a gestational age ≤28 weeks according to the presence or absence of RDS requiring MV, BPD, IVH, or ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP.
  
  
  RESULTS
  In our population 157 infants developed RDS requiring MV, 71 BPD, 70 IVH, and 43 ROP. We found that TC+CC rs2070744 eNOS (41.7 vs. 25.4%, p=0.01) and GT+TT rs1799983 eNOS (51.8 vs. 35.2%, p=0.01) polymorphisms are independent risk factors for BPD. Haplotype reconstruction showed that haplotypes in VEGF and eNOS are significantly associated with different effects on RDS, BPD, IVH, and ROP in our population.
  
  
  CONCLUSIONS
  We found that TC+CC rs2070744 eNOS and GT+TT rs1799983 eNOS polymorphisms are independent predictors of an increased risk of developing BPD. Haplotypes of VEGFA and eNOS may be independent protective or risk markers for prematurity complications.
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Poggi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence - Atherothrombotic Diseases Centre, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gozzini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence - Atherothrombotic Diseases Centre, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Sereni
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence - Atherothrombotic Diseases Centre, Careggi University Hospital of Florence, Florence, Italy; Department of Information Engineering University of Florence, Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Romagnuolo
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence - Atherothrombotic Diseases Centre, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Kura
authors.affiliation: Metabolic and Muscular Unit, Clinic of Pediatric Neurology, Meyer Children's Hospital, Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pasquini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence - Atherothrombotic Diseases Centre, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Child Health, Careggi University Hospital of Florence, Florence, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dani
mesh_terms: D000808:Angiotensinogen / Q000235:genetics; D001997:Bronchopulmonary Dysplasia / Q000150:complications; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D020300:Intracranial Hemorrhages / Q000150:complications; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications; D012178:Retinopathy of Prematurity / Q000150:complications; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C534931:AGT protein, human; C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000808:Angiotensinogen; D052250:Nitric Oxide Synthase Type III; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D007703:Peptidyl-Dipeptidase A