title: Arginase I gene single-nucleotide polymorphism is associated with decreased risk of pulmonary hypertension in bronchopulmonary dysplasia.
abstract: OBJECTIVE
  To test the hypothesis that there are single-nucleotide polymorphisms (SNPs) in genes of the l-arginine/nitric oxide pathway associated with pulmonary hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD).
  
  
  METHODS
  Neonates with BPD were enrolled (n = 140) and clinical characteristics compared between case (BPD + PH) and control (BPD) groups. DNA was isolated from blood leucocytes and assayed for 17 SNPs in l-arginine/nitric oxide pathway genes by Sequenom massarray. Genes included carbamoyl-phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase. SNPs were selected from the National Center for Biotechnology Information database for their putative functionality. Calculated minor allele frequencies (MAF) of cases and controls were compared using χ2 and logistic regression.
  
  
  RESULTS
  Of the 140 patients with BPD, 26% had echocardiographic evidence of PH. Ventilation days were longer for cases than controls (mean 31 vs. 15 days, p < 0.05). Of the 17 SNPs, rs2781666 in arginase I gene was less common in cases (MAF = 0.23) than controls (MAF = 0.37, p = 0.04). The odds of PH decreased by 43% (p = 0.047) for each copy of the SNP minor allele in arginase I gene in patients with BPD.
  
  
  CONCLUSIONS
  Arginase I SNP (rs2781666) may be associated with protection against pulmonary hypertension in preterm neonates 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: J K
authors.initials: JK
authors.lastname: Trittmann
authors.forename: L D
authors.initials: LD
authors.lastname: Nelin
authors.forename: E J
authors.initials: EJ
authors.lastname: Zmuda
authors.forename: J M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.forename: C H
authors.initials: CH
authors.lastname: Backes
authors.forename: J
authors.initials: J
authors.lastname: Frick
authors.forename: P
authors.initials: P
authors.lastname: Vaynshtok
authors.forename: V J
authors.initials: VJ
authors.lastname: Vieland
authors.forename: M A
authors.initials: MA
authors.lastname: Klebanoff
mesh_terms: D001119:Arginase / Q000235:genetics*; D001997:Bronchopulmonary Dysplasia / Q000150:complications*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C574619:ARG1 protein, human; D001119:Arginase
keywords: arginine; argininosuccinate synthase; carbamoyl-phosphate synthetase; nitric oxide synthase; ornithine transcarbamylase