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

Am J Obstet Gynecol. 2010 May;202(5):431.e1-34. doi: 10.1016/j.ajog.2010.03.026.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Case-Control Studies
  • Chile
  • Chorioamnionitis / genetics
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Female
  • Fetal Membranes, Premature Rupture / genetics
  • Genetic Association Studies*
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Haplotypes
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age / physiology
  • Obstetric Labor, Premature / genetics*
  • Polymorphism, Single Nucleotide*
  • Pre-Eclampsia / genetics
  • Pregnancy
  • Premature Birth / genetics
  • Receptors, Interleukin-6 / genetics*
  • Young Adult


  • Receptors, Interleukin-6