RGD Reference Report - Determination of genetic predisposition to patent ductus arteriosus in preterm infants. - Rat Genome Database

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Determination of genetic predisposition to patent ductus arteriosus in preterm infants.

Authors: Dagle, John M  Lepp, Nathan T  Cooper, Margaret E  Schaa, Kendra L  Kelsey, Keegan J P  Orr, Kristin L  Caprau, Diana  Zimmerman, Cara R  Steffen, Katherine M  Johnson, Karen J  Marazita, Mary L  Murray, Jeffrey C 
Citation: Dagle JM, etal., Pediatrics. 2009 Apr;123(4):1116-23. doi: 10.1542/peds.2008-0313.
RGD ID: 401959325
Pubmed: PMID:19336370   (View Abstract at PubMed)
PMCID: PMC2734952   (View Article at PubMed Central)
DOI: DOI:10.1542/peds.2008-0313   (Journal Full-text)


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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanpatent ductus arteriosus susceptibilityIAGP DNA:SNP and haplotype:intron: (rs493694) (human)RGD 
PtgisRatpatent ductus arteriosus susceptibilityISOPTGIS (Homo sapiens)DNA:SNP and haplotype:intron: (rs493694) (human)RGD 
PtgisMousepatent ductus arteriosus susceptibilityISOPTGIS (Homo sapiens)DNA:SNP and haplotype:intron: (rs493694) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanPatent ductus arteriosus susceptibilityIAGP DNA:SNP and haplotype:intron: (rs493694)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information