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

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.

journal_name

Pediatrics

journal_title

Pediatrics

authors

Dagle JM,Lepp NT,Cooper ME,Schaa KL,Kelsey KJ,Orr KL,Caprau D,Zimmerman CR,Steffen KM,Johnson KJ,Marazita ML,Murray JC

doi

10.1542/peds.2008-0313

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

1116-23

issue

4

eissn

0031-4005

issn

1098-4275

pii

123/4/1116

journal_volume

123

pub_type

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