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. METHODOLOGY: 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.
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. METHODOLOGY: 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: M Moser; A Pscherer; C Roth; J Becker; G Mücher; K Zerres; C Dixkens; J Weis; L Guay-Woodford; R Buettner; R Fässler Journal: Genes Dev Date: 1997-08-01 Impact factor: 11.361
Authors: John M Dagle; Kelli K Ryckman; Cassandra N Spracklen; Allison M Momany; C Michael Cotten; Joshua Levy; Grier P Page; Edward F Bell; Waldemar A Carlo; Seetha Shankaran; Ronald N Goldberg; Richard A Ehrenkranz; Jon E Tyson; Barbara J Stoll; Jeffrey C Murray Journal: J Perinatol Date: 2018-12-05 Impact factor: 2.521
Authors: Sydney R Rooney; Elaine L Shelton; Ida Aka; Christian M Shaffer; Ronald I Clyman; John M Dagle; Kelli Ryckman; Tamorah R Lewis; Jeff Reese; Sara L Van Driest; Prince J Kannankeril Journal: Pharmacogenomics Date: 2019-08 Impact factor: 2.533
Authors: Tamorah R Lewis; Elaine L Shelton; Sara L Van Driest; Prince J Kannankeril; Jeff Reese Journal: Semin Fetal Neonatal Med Date: 2018-02-24 Impact factor: 3.926
Authors: Robert B Cotton; Lisa P Shah; Stanley D Poole; Noah J Ehinger; Naoko Brown; Elaine L Shelton; James C Slaughter; H Scott Baldwin; Bibhash C Paria; Jeff Reese Journal: J Mol Cell Cardiol Date: 2013-02-27 Impact factor: 5.000
Authors: Priti M Patel; Allison M Momany; Kendra L Schaa; Paul A Romitti; Charlotte Druschel; Margaret E Cooper; Mary L Marazita; Jeffrey C Murray; John M Dagle Journal: J Pediatr Date: 2016-06-22 Impact factor: 4.406