Genetic variants associated with patent ductus arteriosus in extremely preterm infants

• Type of Material: Article
• Authors: John M. Dagle, University of Iowa; Kelli K. Ryckman, University of Iowa; Cassandra N. Spracklen, University of North Carolina; Allison M. Momany, University of Iowa; C. Michael Cotten, Duke University; Joshua Levy, RTI International, Research Triangle Park, NC; Grier P. Page, Social, Statistical and Environmental Sciences Unit, RTI International, Atlanta, GA; Edward F. Bell, University of Iowa; Waldemar A. Carlo, University of Alabama Birmingham; Seetha Shankaran, Wayne State University; Ronald N. Goldberg, Duke University; Richard A. Ehrenkranz, Yale University; Jon E. Tyson, University of Texas Houston; Barbara Stoll, Emory University; Jeffrey C. Murray, University of Iowa; Brenda Poindexter, Emory University
• Language: English
• Date: 2019-03-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Springer Nature America, Inc. 2018.
• Final Published Version (URL): http://dx.doi.org/10.1038/s41372-018-0285-6
• Title of Journal or Parent Work: Journal of Perinatology
• Volume: 39
• Issue: 3
• Start Page: 401
• End Page: 408
• Grant/Funding Information: National Center for Research Resources (General Clinical Research Center grants M01 RR30, M01 RR32, M01 RR39, M01 RR70, M01 RR80, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01 RR7122, M01 RR8084, M01 RR16587) provided grant support for the Neonatal Research Network’s Glutamine trial which included the Genomic Study through cooperative agreements.; Financial Support: Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, 5U10 HD040492–12; RO1HL109199 NIH (JD); 6-FY11–261 and 21-FY13–19 March of Dimes (JM) and individual grant numbers from sites within the NRN are included below.; The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (grants U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40689)
• Keywords: Risk; Expression; Retinopathy; Endothelial growth factor; Injury; Profiles; Pediatrics; Indomethacin; Closure; Outcomes; Prematurity; Obstetrics & Gynecology; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Health Sciences, Obstetrics and Gynecology; Environmental Sciences; Biology, Genetics

Abstract

Objective: Patent ductus arteriosus (PDA) is a commonly observed condition in preterm infants. Prior studies have suggested a role for genetics in determining spontaneous ductal closure. Using samples from a large neonatal cohort we tested the hypothesis that common genetic variations are associated with PDA in extremely preterm infants. Study design: Preterm infants (n = 1013) enrolled at NICHD Neonatal Research Network sites were phenotyped for PDA. DNA was genotyped for 1634 single nucleotide polymorphisms (SNPs) from candidate genes. Analyses were adjusted for ancestral eigenvalues and significant epidemiologic variables. Results: SNPs in several genes were associated with the clinical diagnosis of PDA and with surgical ligation in extremely preterm neonates diagnosed with PDA (p < 0.01). None of the associations were significant after correction for multiple comparisons. Conclusion: We identified several common genetic variants associated with PDA. These findings may inform further studies on genetic risk factors for PDA in preterm infants.