Abstract
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.
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Acknowledgements
We express our sincere thanks to the families that participated in this study. Their enthusiasm and support for the project was inspiring. We also thank Susan Berends, Elise Bream, Diedre Fleener, and Laura Knosp for their invaluable assistance; Tamara Busch and Elizabeth Leslie for assistance with sequencing; Stanton Berberich, Franklin Delin, and Dari Shirazi from the State Hygienic Laboratory for their help with the Newborn Screen data; Jeffrey Segar for his comments; and the entire staff of the University of Iowa Children’s Hospital Newborn Intensive Care Unit for their tireless dedication to the patients and their support of this project.
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Byers, H., Dagle, J., Klein, J. et al. Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn. Pediatr Res 71, 162–167 (2012). https://doi.org/10.1038/pr.2011.24
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DOI: https://doi.org/10.1038/pr.2011.24
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