Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

Roberto Romero, Digna R. Velez Edwards, Juan Pedro Kusanovic, Sonia S. Hassan, Shali Mazaki-Tovi, Edi Vaisbuch, Chong Jai Kim, Tinnakorn Chaiworapongsa, Brad D. Pearce, Lara A. Friel, Jacquelaine Bartlett, Madan Kumar Anant, Benjamin A. Salisbury, Gerald F. Vovis, Min Seob Lee, Ricardo Gomez, Ernesto Behnke, Enrique Oyarzun, Gerard Tromp, Scott M. WilliamsRamkumar Menon

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Objective: The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery. Study Design: A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing. Results: The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P = .000148) and tissue inhibitor of metalloproteinase 2 (mother; P = .000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P = .004 and .007, respectively). Conclusion: An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.

Original languageEnglish (US)
Pages (from-to)431.e1-431.e34
JournalAmerican journal of obstetrics and gynecology
Volume202
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • chorioamnionitis
  • DNA variants
  • extracellular matrix
  • genetic association study
  • genotype
  • haplotype
  • IL-6
  • parturition
  • SNP

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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    Romero, R., Velez Edwards, D. R., Kusanovic, J. P., Hassan, S. S., Mazaki-Tovi, S., Vaisbuch, E., Kim, C. J., Chaiworapongsa, T., Pearce, B. D., Friel, L. A., Bartlett, J., Anant, M. K., Salisbury, B. A., Vovis, G. F., Lee, M. S., Gomez, R., Behnke, E., Oyarzun, E., Tromp, G., ... Menon, R. (2010). Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes. American journal of obstetrics and gynecology, 202(5), 431.e1-431.e34. https://doi.org/10.1016/j.ajog.2010.03.026