A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)

Am J Obstet Gynecol. 2010 Oct;203(4):361.e1-361.e30. doi: 10.1016/j.ajog.2010.05.026. Epub 2010 Jul 31.

Abstract

Objective: We sought to determine whether maternal/fetal single-nucleotide polymorphisms (SNPs) in candidate genes are associated with preterm prelabor rupture of membranes (pPROM).

Study design: A case-control study was conducted in patients with pPROM (225 mothers and 155 fetuses) and 599 mothers and 628 fetuses with a normal pregnancy; 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; false discovery rate was used to correct for multiple testing (q* = 0.15).

Results: First, a SNP in tissue inhibitor of metalloproteinase 2 in mothers was significantly associated with pPROM (odds ratio, 2.12; 95% confidence interval, 1.47-3.07; P = .000068), and this association remained significant after correction for multiple comparisons. Second, haplotypes for Alpha 3 type IV collagen isoform precursor in the mother were associated with pPROM (global P = .003). Third, multilocus analysis identified a 3-locus model, which included maternal SNPs in collagen type I alpha 2, defensin alpha 5 gene, and endothelin 1.

Conclusion: DNA variants in a maternal gene involved in extracellular matrix metabolism doubled the risk of pPROM.

Publication types

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

MeSH terms

  • Adult
  • Autoantigens / genetics
  • Case-Control Studies
  • Chorioamnionitis / pathology
  • Collagen / genetics
  • Collagen Type I
  • Collagen Type IV / genetics
  • Endothelin-1 / genetics
  • Female
  • Fetal Membranes, Premature Rupture / genetics*
  • Fetus
  • Gene Frequency
  • Genetic Association Studies*
  • Genotype
  • Haplotypes
  • Humans
  • Infant, Newborn
  • Male
  • Models, Genetic
  • Mothers
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Procollagen
  • Protein Isoforms
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Prostaglandin E / genetics
  • Receptors, Prostaglandin E, EP1 Subtype
  • Sequence Analysis, DNA
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • alpha-Defensins / genetics

Substances

  • Autoantigens
  • Collagen Type I
  • Collagen Type IV
  • Endothelin-1
  • PTGER1 protein, human
  • Procollagen
  • Protein Isoforms
  • Receptors, Corticotropin-Releasing Hormone
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype
  • alpha-Defensins
  • type IV collagen alpha3 chain
  • Tissue Inhibitor of Metalloproteinase-2
  • Collagen