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Single Nucleotide Polymorphisms in the Human Progesterone Receptor Gene and Spontaneous Preterm Birth

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Thomas Morgan, MD

Department of Pediatrics, Washington University, St Louis, Missouri

Mert O. Bahtiyar, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Victoria V. Snegovskikh, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Frederick Schatz, PhD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Edward Kuczynski, PhD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Edmund F. Funai, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Antonette T. Dulay, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Se-Te Joseph Huang, MD, PhD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Catalin S. Buhimschi, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Irina A. Buhimschi, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Stephen J. Fortunato, MD, PhD

Perinatal Research Center, Nashville, Tennessee

Ramkumar Menon, PhD

Perinatal Research Center, Nashville, Tennessee

Charles J. Lockwood, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Errol R. Norwitz, MD, PhD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, errol.norwitz{at}yale.edu

Progesterone supplementation can prevent preterm birth in some high-risk women. Progesterone binds to progesterone receptor (PR) and modulates the expression of target genes. This study investigates the association between single nucleotide polymorphisms (SNPs) in the PR gene and spontaneous preterm birth. DNA was extracted from consecutive patients with preterm birth (n = 78) and term controls (n = 415), and genotyping was performed for 3 PR SNPs (+331[G>A], + 770[C>T], +660[G>T]) using Sequenom matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed by ² test and logistic regression analysis. Multivariate analysis showed no association between maternal carriage of minor + 331T, +770T, and/or +660T alleles and preterm birth when controlled for maternal age, ethnicity, gravidity, parity, prior preterm birth, route of delivery, or neonatal outcome. Carriage of +770T and +660T (but not +331T) was associated with preterm birth in women with a body mass index <18.5 kg/m² (relative risk, 10.8; 95% confidence interval, 1.4-82.6; P = .02). Maternal carriage of minor alleles of +331(G>A), +770(C>T), and +660(G> T) SNPs in the PR gene is not associated with spontaneous preterm birth.

Key Words: Preterm birth • progresterone,progesterone receptor • single nucleotide polymorphisms • human pregnancy.

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