title: A single nucleotide polymorphism in the dimethylarginine dimethylaminohydrolase gene is associated with lower risk of pulmonary hypertension in bronchopulmonary dysplasia.
abstract: OBJECTIVE
  Pulmonary hypertension (PH) develops in 25-40% of bronchopulmonary dysplasia (BPD) patients, substantially increasing mortality. We have previously found that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) production, is elevated in patients with BPD-associated PH. ADMA is metabolised by N(ᴳ) ,N(ᴳ) -dimethylarginine dimethylaminohydrolase (DDAH). Presently, we test the hypothesis that there are single nucleotide polymorphisms (SNPs) in DDAH1 and/or DDAH2 associated with the development of PH in BPD patients.
  
  
  METHODS
  BPD patients were enrolled (n = 98) at Nationwide Children's Hospital. Clinical characteristics and 36 SNPs in DDAH1 and DDAH2 were compared between BPD-associated PH patients (cases) and BPD-alone patients (controls).
  
  
  RESULTS
  In BPD patients, 25 (26%) had echocardiographic evidence of PH (cases). In this cohort, DDAH1 wild-type rs480414 was 92% sensitive and 53% specific for PH in BPD, and the DDAH1 SNP rs480414 decreased the risk of PH in an additive model of inheritance (OR = 0.39; 95% CI [0.18-0.88], p = 0.01).
  
  
  CONCLUSIONS
  The rs480414 SNP in DDAH1 may be protective against the development of PH in patients with BPD. Furthermore, the DDAH1 rs480414 may be a useful biomarker in developing predictive models for PH in patients with BPD.
authors.affiliation: Ohio Perinatal Research Network, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Trittmann
authors.affiliation: Department of Pediatrics, The Ohio State University, Columbus, OH, USA.|Cytogenetics/Molecular Genetics Laboratory at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: Cytogenetics/Molecular Genetics Laboratory at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Zmuda
authors.affiliation: Cytogenetics/Molecular Genetics Laboratory at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Frick
authors.affiliation: Ohio Perinatal Research Network, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Rogers
authors.affiliation: Department of Pediatrics, The Ohio State University, Columbus, OH, USA.|Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Vieland
authors.affiliation: Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
authors.forename: Louis G
authors.initials: LG
authors.lastname: Chicoine
authors.affiliation: Ohio Perinatal Research Network, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
authors.forename: Leif D
authors.initials: LD
authors.lastname: Nelin
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D001997:Bronchopulmonary Dysplasia / Q000150:complications*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D000581:Amidohydrolases; C059999:dimethylargininase
keywords: Neonate; Nitric oxide; Prematurity; Urea