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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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, 1.473.07; 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.

Original languageEnglish
Pages (from-to)361.e1-361.e30
JournalAmerican Journal of Obstetrics and Gynecology
Issue number4
StatePublished - Oct 2010
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported, in part, by the Perinatology Research Branch , Division of Intramural Research , Eunice Kennedy Shriver National Institute of Child Health and Human Development , National Institutes of Health , Department of Health and Human Services .


  • DNA variants
  • chorioamnionitis
  • extracellular matrix
  • genetic association study
  • genomics
  • genotype
  • haplotype
  • high dimensional biology
  • matrix metalloproteinase
  • parturition
  • prematurity
  • preterm prelabor rupture of membranes
  • single-nucleotide polymorphism


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