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Pediatr Res. 2016 May;79(5):776-80. doi: 10.1038/pr.2016.7. Epub 2016 Jan 13.

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

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Department of Pediatrics, University of Iowa, Iowa City, Iowa.
Department of Genetics, Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina.
Department of Neonatology, Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes, San Miguel de Tucumán, Argentina.
Department of Epidemiology, University of Southern Denmark, Odense, Denmark.
Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa.



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.

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