Journal article
Determination of Genetic Predisposition to Patent Ductus Arteriosus in Preterm Infants
Pediatrics (Evanston), Vol.123(4), pp.1116-1123
04/2009
DOI: 10.1542/peds.2008-0313
PMCID: PMC2734952
PMID: 19336370
Abstract
Patent ductus arteriosus (PDA) is a common morbidity associated with preterm birth. The incidence of PDA increases with decreasing gestational age to about 70% in infants born at 25 weeks gestation. Although medical treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is used to close the ductus arteriosus, approximately 30% of infants with a PDA do not respond to pharmacologic attempts at closure. We investigated whether single nucleotide polymorphisms (SNPs) in genes that regulate smooth muscle contraction, xenobiotic detoxification, inflammation and other processes are markers for persistent patency of the DA. Initially, 377 SNPs from 130 genes of interest were evaluated in DNA samples collected from 204 infants with a gestational age of less than 32 weeks. A family-based association test (FBAT) was performed on genotyping data to evaluate over-transmission of alleles. P-values of less than 0.01 were detected for genetic variations found in seven genes. The analysis was then replicated with an independent set of 162 infants, focusing on the seven markers with initial p-values less than 0.01, and one genetic variant in the angiotensin II type I receptor
(AGTR1)
previously shown to be related to PDA. Of the initial positive signals, SNPs in the transcription factor AP-2 beta (
TFAP2B
) and TNF receptor-associated factor 1 (
TRAF1
) genes remained significant, both with p-values of 0.005. An
AGTR1
polymorphism previously reported to be associated with PDA following prophylactic indomethacin administration was not associated with the presence of a PDA in our population (p = 0.48). Overall, our data support a role for a genetic contribution to the risk of PDAs in preterm infants.
Details
- Title: Subtitle
- Determination of Genetic Predisposition to Patent Ductus Arteriosus in Preterm Infants
- Creators
- John M Dagle - Department of Pediatrics, University of Iowa, Iowa City, IA. United States 52242Nathan T Lepp - Department of Pediatrics, University of Iowa, Iowa City, IA. United States 52242Margaret E Cooper - Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, United States 15219Kendra L Schaa - Department of Pediatrics, University of Iowa, Iowa City, IA. United States 52242Keegan JP Kelsey - Department of Pediatrics, University of Iowa, Iowa City, IA. United States 52242Kristin L Orr - University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA. United States 52242Diana Caprau - Department of Pediatrics, University of Iowa, Iowa City, IA. United States 52242Cara R Zimmerman - University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA. United States 52242Katherine M Steffen - University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA. United States 52242Karen J Johnson - Department of Pediatrics, University of Iowa, Iowa City, IA. United States 52242Mary L Marazita - Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, PA, United States 15219Jeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IA. United States 52242
- Resource Type
- Journal article
- Publication Details
- Pediatrics (Evanston), Vol.123(4), pp.1116-1123
- DOI
- 10.1542/peds.2008-0313
- PMID
- 19336370
- PMCID
- PMC2734952
- NLM abbreviation
- Pediatrics
- ISSN
- 0031-4005
- eISSN
- 1098-4275
- Publisher
- American Academy of Pediatrics
- Language
- English
- Date published
- 04/2009
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Obstetrics and Gynecology; Biochemistry and Molecular Biology; Dental Research; Neonatology
- Record Identifier
- 9984025258202771
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