Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth

Dinushan C Kaluarachchi; Allison M Momany; Tamara D Busch; Lucas G Gimenez; Cesar Saleme; Viviana Cosentino; Kaare Christensen; John M Dagle; Kelli K Ryckman; Jeffrey C Murray

doi:10.1038/pr.2016.7

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Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth

Journal article

Open access

Peer reviewed

Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth

Dinushan C Kaluarachchi, Allison M Momany, Tamara D Busch, Lucas G Gimenez, Cesar Saleme, Viviana Cosentino, Kaare Christensen, John M Dagle, Kelli K Ryckman and Jeffrey C Murray

Pediatric research, Vol.79(5), pp.776-780

05/2016

DOI: 10.1038/pr.2016.7

PMCID: PMC6596415

PMID: 26761123

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Abstract

Preterm birth (PTB) is a major cause of neonatal mortality and morbidity. There is strong evidence of genetic susceptibility. Objective of this study was to identify genetic variants contributing to PTB. Genotyping was performed for 24 single nucleotide polymorphisms (SNPs) in 4 candidate genes (NR5A2, FSHR, FOXP3, and SERPINH1). Genotyping was completed on 728 maternal triads (mother and maternal grandparents of a preterm infant). Data were analyzed with Family Based Association Test. For all maternal triads rs2737667 of NR5A2 showed significant association at P = 0.02. When stratifying by gestational age three SNPs in NR5A2 had P values <0.05 in the <32-wk gestational age group (rs12131233, P = 0.007; rs2737667, P = 0.04; rs2816949, P = 0.02). When preterm premature rupture of membranes cases were excluded rs2737667 of NR5A2 showed the strongest association with a P value <0.0002. This association remained significant after correction for multiple testing. This study suggests a potential association between intronic SNPs in the NR5A2 gene and PTB. NR5A2 gene encodes for the liver receptor homolog-1 protein, which plays a critical role in regulation of cholesterol metabolism, steroidogenesis, and progesterone synthesis. These findings suggest that NR5A2 may be important in the pathophysiology of PTB and exploring noncoding regulators of NR5A2 is warranted.

Haplotypes

Argentina

Genetic Predisposition to Disease

Premature Birth - genetics

United States

Humans

Genotype

Receptors, Cytoplasmic and Nuclear - physiology

Receptors, Cytoplasmic and Nuclear - genetics

Gestational Age

Pregnancy

Denmark

Female

Polymorphism, Single Nucleotide

Infant, Newborn

Details

Title: Subtitle: Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth
Creators: Dinushan C Kaluarachchi - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Allison M Momany - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Tamara D Busch - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Lucas G Gimenez - Department of Genetics, Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina
Cesar Saleme - Department of Neonatology, Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes, San Miguel de Tucumán, Argentina
Viviana Cosentino - Department of Genetics, Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina
Kaare Christensen - Department of Epidemiology, University of Southern Denmark, Odense, Denmark
John M Dagle - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Kelli K Ryckman - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
Jeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Pediatric research, Vol.79(5), pp.776-780
DOI: 10.1038/pr.2016.7
PMID: 26761123
PMCID: PMC6596415
NLM abbreviation: Pediatr Res
ISSN: 1530-0447
eISSN: 1530-0447
Publisher: United States
Grant note: R01 HD057192 / NICHD NIH HHS R01 HD052953 / NICHD NIH HHS
Language: English
Date published: 05/2016
Academic Unit: Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Epidemiology; Iowa Neuroscience Institute; Pediatric Dentistry; Craniofacial Anomalies Research Center; Nursing; Public Policy Center (Archive); Biochemistry and Molecular Biology; Dental Research; Neonatology
Record Identifier: 9983995129102771

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