title: A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM).
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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  DNA variants in a maternal gene involved in extracellular matrix metabolism doubled the risk of pPROM.
authors.affiliation: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health/Department of Health and Human Services, Bethesda, MD, USA. prbchiefstaff@med.wayne.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Lara A
authors.initials: LA
authors.lastname: Friel
authors.forename: Digna R
authors.initials: DR
authors.lastname: Velez Edwards
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Shali
authors.initials: S
authors.lastname: Mazaki-Tovi
authors.forename: Edi
authors.initials: E
authors.lastname: Vaisbuch
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Offer
authors.initials: O
authors.lastname: Erez
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Brad D
authors.initials: BD
authors.lastname: Pearce
authors.forename: Jacquelaine
authors.initials: J
authors.lastname: Bartlett
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Salisbury
authors.forename: Madan Kumar
authors.initials: MK
authors.lastname: Anant
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Vovis
authors.forename: Min Seob
authors.initials: MS
authors.lastname: Lee
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gomez
authors.forename: Ernesto
authors.initials: E
authors.lastname: Behnke
authors.forename: Enrique
authors.initials: E
authors.lastname: Oyarzun
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000235:genetics; D016022:Case-Control Studies; D002821:Chorioamnionitis / Q000473:pathology; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I; D024141:Collagen Type IV / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics*; D005333:Fetus; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008957:Models, Genetic; D009035:Mothers; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011347:Procollagen; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000235:genetics; D058306:Receptors, Prostaglandin E, EP1 Subtype; D017422:Sequence Analysis, DNA; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D023084:alpha-Defensins / Q000235:genetics
chemical_list: D001324:Autoantigens; D024042:Collagen Type I; D024141:Collagen Type IV; D019332:Endothelin-1; C545635:PTGER1 protein, human; D011347:Procollagen; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D023084:alpha-Defensins; C057112:type IV collagen alpha3 chain; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen