title: Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn.
abstract: BACKGROUND
  Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant morbidity and mortality. Recently, genetic associations have been found in idiopathic pulmonary arterial hypertension.
  
  
  RESULTS
  PPHN was significantly (P < 0.05) associated with genetic variants in corticotropin-releasing hormone (CRH) receptor 1, CRHR1 and CRH-binding protein, CRHBP. Association with CRHR1 rs4458044 passed the Bonferroni threshold for significance. No mutations were found in the bone morphogenetic protein receptor type II (BMPR2) gene.
  
  
  CONCLUSIONS
  We describe previously unreported genetic associations between PPHN and CRHR1 and CRHBP. These findings may have implications for further understanding the pathophysiology of PPHN and treatment.
  
  
  METHODS
  We performed a family-based candidate gene study to examine a genetic association with PPHN and sequenced the BMPR2 gene in 72 individuals. We enrolled 110 families with infants diagnosed with PPHN based on inclusion criteria. After medical chart review, 22 subjects were excluded based on predefined criteria, and DNA samples from 88 affected infants and at least one parent per infant were collected and genotyped. Thirty-two single-nucleotide polymorphisms in 12 genes involved in vasoconstriction/vasodilation, lung development, surfactant regulation, or vascular endothelial cell function were investigated using family-based association tests.
authors.affiliation: Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Byers
authors.forename: John M
authors.initials: JM
authors.lastname: Dagle
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Klein
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
authors.forename: Erin L
authors.initials: EL
authors.lastname: McDonald
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Borowski
mesh_terms: D000328:Adult; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007484:Iowa; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D010547:Persistent Fetal Circulation Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult; D000099052:CRF Receptor, Type 1
chemical_list: D002352:Carrier Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein; D000099052:CRF Receptor, Type 1; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II