Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression

Nahid Waleh; Anne Marie Barrette; John M Dagle; Allison Momany; Chengshi Jin; Nancy K Hills; Elaine L Shelton; Jeff Reese; Ronald I Clyman

doi:10.1016/j.jpeds.2015.07.011

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Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression

Journal article

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Peer reviewed

Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression

Nahid Waleh, Anne Marie Barrette, John M Dagle, Allison Momany, Chengshi Jin, Nancy K Hills, Elaine L Shelton, Jeff Reese and Ronald I Clyman

The Journal of pediatrics, Vol.167(5), pp.1033-1041.e2

11/2015

DOI: 10.1016/j.jpeds.2015.07.011

PMCID: PMC4661123

PMID: 26265282

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Abstract

To identify genes affected by advancing gestation and racial/ethnic origin in human ductus arteriosus (DA). We collected 3 sets of DA tissue (n = 93, n = 89, n = 91; total = 273 fetuses) from second trimester pregnancies. We examined four genes, with DNA polymorphisms that distribute along racial lines, to identify "Caucasian" and "non-Caucasian" DA. We used real time polymerase chain reaction to measure RNA expression of 48 candidate genes involved in functional closure of the DA, and used multivariable regression analyses to examine the relationships between advancing gestation, "non-Caucasian" race, and gene expression. Mature gestation and non-Caucasian race are significant predictors for identifying infants who will close their patent DA when treated with indomethacin. Advancing gestation consistently altered gene expression in pathways involved with oxygen-induced constriction (eg, calcium-channels, potassium-channels, and endothelin signaling), contractile protein maturation, tissue remodeling, and prostaglandin and nitric oxide signaling in all 3 tissue sets. None of the pathways involved with oxygen-induced constriction appeared to be altered in "non-Caucasian" DA. Two genes, SLCO2A1 and NOS3, (involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively) were consistently decreased in "non-Caucasian" DA. Prostaglandins and nitric oxide are the most important vasodilators opposing DA closure. Indomethacin inhibits prostaglandin production, but not nitric oxide production. Because decreased SLCO2A1 and NOS3 expression can lead to increased prostaglandin and decreased nitric oxide concentrations, we speculate that prostaglandin-mediated vasodilation may play a more dominant role in maintaining the "non-Caucasian" patent DA, making it more likely to close when inhibited by indomethacin.

Pregnancy Trimester, Second

Ductus Arteriosus, Patent - drug therapy

Humans

Ductus Arteriosus, Patent - ethnology

Organic Anion Transporters - metabolism

Oxygen - metabolism

Organic Anion Transporters - genetics

Indomethacin - therapeutic use

Time Factors

Gene Expression Regulation, Developmental

Polymerase Chain Reaction

Female

Nitric Oxide Synthase Type III - metabolism

Continental Population Groups

Ductus Arteriosus, Patent - genetics

Signal Transduction

Ductus Arteriosus - metabolism

Genotype

Gestational Age

Nitric Oxide Synthase Type III - genetics

Ductus Arteriosus - embryology

Polymorphism, Genetic

Aorta - pathology

Pregnancy

Regression Analysis

DNA

Details

Title: Subtitle: Effects of Advancing Gestation and Non-Caucasian Race on Ductus Arteriosus Gene Expression
Creators: Nahid Waleh - Biosciences Division, SRI International, Menlo Park, CA
Anne Marie Barrette - Cardiovascular Research Institute and Department of Pediatrics, University of California San Francisco, San Francisco, CA
John M Dagle - Department of Pediatrics, University of Iowa, Iowa City, IA
Allison Momany - Department of Pediatrics, University of Iowa, Iowa City, IA
Chengshi Jin - Department of Neurology, University of California San Francisco, San Francisco, CA
Nancy K Hills - Department of Neurology, University of California San Francisco, San Francisco, CA
Elaine L Shelton - Department of Pediatrics, Vanderbilt University, Nashville, TN
Jeff Reese - Department of Pediatrics, Vanderbilt University, Nashville, TN
Ronald I Clyman - Cardiovascular Research Institute and Department of Pediatrics, University of California San Francisco, San Francisco, CA. Electronic address: clymanr@peds.ucsf.edu
Resource Type: Journal article
Publication Details: The Journal of pediatrics, Vol.167(5), pp.1033-1041.e2
DOI: 10.1016/j.jpeds.2015.07.011
PMID: 26265282
PMCID: PMC4661123
NLM abbreviation: J Pediatr
ISSN: 0022-3476
eISSN: 1097-6833
Publisher: United States
Grant note: R01 HL109199 / NHLBI NIH HHS T32 GM108540 / NIGMS NIH HHS HL109199 / NHLBI NIH HHS
Language: English
Date published: 11/2015
Academic Unit: Stead Family Department of Pediatrics; Epidemiology; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Neonatology
Record Identifier: 9984025270202771

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