Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Apr;123(4):1116-23.
doi: 10.1542/peds.2008-0313.

Determination of Genetic Predisposition to Patent Ductus Arteriosus in Preterm Infants

Affiliations
Free PMC article

Determination of Genetic Predisposition to Patent Ductus Arteriosus in Preterm Infants

John M Dagle et al. Pediatrics. .
Free PMC article

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.

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.

Figures

Figure 1
Figure 1
Frequency distribution of the 366 study infants by gestational age.
Figure 2
Figure 2
Results of the family-based test (FBAT) for genetic association with PDA. The negative log of the p-value is plotted for each SNPs association with PDA. SNP signals reaching about the dotted line represent p-values less than 0.01.
Figure 3
Figure 3
Haplotype analysis for association with PDA in the TFAP2B, TRAF1, and PTGIS genes. Haplotypes for three genes were analyzed using a 2-SNP window (TFAP2B and PTGIS) or a combination of 2-, 3- and 4-SNP windows (TRAF1). Allele combinations yielding an individual haplotype with a p-value less than 0.05 are shaded gray. The sign in parentheses after the p value indicates whether the allele combination is positively or negatively associated with PDA.

Similar articles

See all similar articles

Cited by 18 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback