Details

Autor(en) / Beteiligte

• 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

Titel

Determination of genetic predisposition to patent ductus arteriosus in preterm infants

Ist Teil von

• Pediatrics (Evanston), 2009-04, Vol.123 (4), p.1116

Ort / Verlag

United States

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.