title: Determination of genetic predisposition to patent ductus arteriosus in preterm infants.
abstract: OBJECTIVE
  Patent ductus arteriosus is a common morbidity associated with preterm birth. The incidence of patent ductus arteriosus increases with decreasing gestational age to approximately 70% in infants born at 25 weeks' gestation. Our major goal was to determine if genetic risk factors play a role in patent ductus arteriosus seen in preterm infants.
  
  
  METHODS
  We investigated whether single-nucleotide polymorphisms in genes that regulate smooth muscle contraction, xenobiotic detoxification, inflammation, and other processes are markers for persistent patency of ductus arteriosus. Initially, 377 single-nucleotide polymorphisms from 130 genes of interest were evaluated in DNA samples collected from 204 infants with a gestational age of <32 weeks. A family-based association test was performed on genotyping data to evaluate overtransmission of alleles.
  
  
  RESULTS
  P values of <.01 were detected for genetic variations found in 7 genes. This prompted additional analysis with an additional set of 162 infants, focusing on the 7 markers with initial P values of <.01, and 1 genetic variant in the angiotensin II type I receptor previously shown to be related to patent ductus arteriosus. Of the initial positive signals, single-nucleotide polymorphisms in the transcription factor AP-2 beta and tumor necrosis factor receptor-associated factor 1 genes remained significant. Additional haplotype analysis revealed genetic variations in prostacyclin synthase to be associated with patent ductus arteriosus. An angiotensin II type I receptor polymorphism previously reported to be associated with patent ductus arteriosus after prophylactic indomethacin administration was not associated with the presence of a patent ductus arteriosus in our population.
  
  
  CONCLUSIONS
  Overall, our data support a role for genetic variations in transcription factor AP-2 beta, tumor necrosis factor receptor-associated factor 1, and prostacyclin synthase in the persistent patency of the ductus arteriosus seen in preterm infants.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. john-dagle@uiowa.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Dagle
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Lepp
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Schaa
authors.forename: Keegan J P
authors.initials: KJ
authors.lastname: Kelsey
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Orr
authors.forename: Diana
authors.initials: D
authors.lastname: Caprau
authors.forename: Cara R
authors.initials: CR
authors.lastname: Zimmerman
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Steffen
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Johnson
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray