title: Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA. prbchiefstaff@med.wayne.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
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: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Brad D
authors.initials: BD
authors.lastname: Pearce
authors.forename: Lara A
authors.initials: LA
authors.lastname: Friel
authors.forename: Jacquelaine
authors.initials: J
authors.lastname: Bartlett
authors.forename: Madan Kumar
authors.initials: MK
authors.lastname: Anant
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Salisbury
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; D016022:Case-Control Studies; D002677:Chile; D002821:Chorioamnionitis / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D055815:Young Adult
chemical_list: D019947:Receptors, Interleukin-6
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