Document Detail

Determination of genetic predisposition to patent ductus arteriosus in preterm infants.
MedLine Citation:
PMID:  19336370     Owner:  NLM     Status:  MEDLINE    
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.
John M Dagle; Nathan T Lepp; Margaret E Cooper; Kendra L Schaa; Keegan J P Kelsey; Kristin L Orr; Diana Caprau; Cara R Zimmerman; Katherine M Steffen; Karen J Johnson; Mary L Marazita; Jeffrey C Murray
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatrics     Volume:  123     ISSN:  1098-4275     ISO Abbreviation:  Pediatrics     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-04-28     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0376422     Medline TA:  Pediatrics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1116-23     Citation Subset:  AIM; IM    
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MeSH Terms
Cholesterol Ester Transfer Proteins / genetics
Cytochrome P-450 CYP2D6 / genetics
Cytochrome P-450 Enzyme System / genetics
Ductus Arteriosus, Patent / genetics*
Genetic Predisposition to Disease / epidemiology*
Gestational Age
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases / genetics*
Intramolecular Oxidoreductases / genetics
Lipase / genetics
Polymorphism, Single Nucleotide*
Receptor, Angiotensin, Type 1 / genetics
Receptors, Corticotropin-Releasing Hormone / genetics
TNF Receptor-Associated Factor 1 / genetics
Transcription Factor AP-2 / genetics
Grant Support
M01 RR000059/RR/NCRR NIH HHS; M01 RR000059-466795/RR/NCRR NIH HHS; P30 ES005605/ES/NIEHS NIH HHS; P30 ES005605-170010/ES/NIEHS NIH HHS; P30 ES005605-180010/ES/NIEHS NIH HHS; P30 ES05605/ES/NIEHS NIH HHS; R01 HD052953/HD/NICHD NIH HHS; R01 HD052953-01/HD/NICHD NIH HHS; R01 HD052953-01/HD/NICHD NIH HHS; T32 HD041922/HD/NICHD NIH HHS; T32 HD041922/HD/NICHD NIH HHS; T32 HD041922-02/HD/NICHD NIH HHS
Reg. No./Substance:
0/CETP protein, human; 0/CRF receptor type 1; 0/Cholesterol Ester Transfer Proteins; 0/Receptor, Angiotensin, Type 1; 0/Receptors, Corticotropin-Releasing Hormone; 0/TFAP2B protein, human; 0/TNF Receptor-Associated Factor 1; 0/Transcription Factor AP-2; 9035-51-2/Cytochrome P-450 Enzyme System; EC P-450 CYP2D6; EC; EC 5.3.-/Intramolecular Oxidoreductases; EC synthetase

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