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Evidence of a gene–environment interaction of NODAL variants and inflammation in preterm birth



NODAL has been implicated in timing of parturition and immune regulation. We investigated the relationship between NODAL polymorphisms, infection/inflammation, and preterm birth.

Study design

For this secondary analysis, 613 women (189 preterm and 424 term) from the Montreal Prematurity Study were genotyped for NODAL polymorphisms and assessed for bacterial vaginosis and placental inflammation.


NODAL polymorphisms were not associated with preterm birth. However, the rs2231947(C>T) variant allele was associated with increased risk for preterm birth among women with bacterial vaginosis (odds ratio: 2.76, 95% confidence interval: 1.12−6.85). Among women without placental inflammation, the rs1904589(A>G) variant allele was associated with increased risk of preterm birth (odds ratio: 1.31, 95% confidence interval: 1.02−1.70). Among women with placental inflammation, the rs10999338(C>T) variant allele was associated with reduced risk of preterm birth (odds ratio: 0.50, 95% confidence interval: 0.29−0.87).


The effect of NODAL polymorphisms on preterm birth depends on maternal infection/inflammation status.

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We thank Michael Kramer, Mourad Dahhou, and the members of the Montreal Prematurity Study Group. We also thank the McGill University and Genome Quebec Innovation Centre (Montreal, Canada) for performing SNP discovery and Sanger sequencing. We thank all of the women for their generous participation in this study.


This study was funded by March of Dimes Grant No. 21-FY14-130. LMS was supported by a Toronto Dominion Bank Post-Doctoral Fellowship for Child Health Research Excellence. TH was supported by the Ministry of Higher Education of Saudi Arabia. Support for the Montreal Prematurity Study was provided by the Perinatal Epidemiological Research Iniviative Program Grant No 20-FY04-38 from the March of Dimes Birth Defects Foundation. The funders had no role in study design, data collection and analysis, interpretation of data, decision to publish, or preparation of the manuscript.

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Correspondence to Daniel Dufort.

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Starr, L.M., Heba, T. & Dufort, D. Evidence of a gene–environment interaction of NODAL variants and inflammation in preterm birth. J Perinatol 38, 482–488 (2018).

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