Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn

Pediatr Res. 2012 Feb;71(2):162-7. doi: 10.1038/pr.2011.24. Epub 2011 Dec 21.


Introduction: 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.

Discussion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Bone Morphogenetic Protein Receptors, Type II / genetics
  • Carrier Proteins / genetics
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Iowa
  • Linear Models
  • Linkage Disequilibrium
  • Male
  • Pedigree
  • Persistent Fetal Circulation Syndrome / genetics*
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Retrospective Studies
  • Young Adult


  • Carrier Proteins
  • Receptors, Corticotropin-Releasing Hormone
  • corticotropin releasing factor-binding protein
  • CRF receptor type 1
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II