1394

CRHR1

CRF-R|CRF-R-1|CRF-R1|CRF1|CRFR-1|CRFR1|CRH-R-1|CRH-R1|CRH-R1h|CRHR|CRHR1L|CRHR1f;corticotropin releasing hormone receptor 1;CRHR1;corticotropin releasing hormone receptor 1

corticotropin releasing hormone receptor variant 1e|corticotropin releasing hormone receptor variant 1g|corticotropin-releasing factor receptor 1|corticotropin-releasing factor type 1 receptor|corticotropin-releasing hormone receptor 1|seven transmembrane

17q12-q22

protein-coding

Count: CRHR1; 1394

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.