title: Polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, local midtrimester cytokine response to vaginal flora, and subsequent preterm birth.
abstract: OBJECTIVE
  This study investigated the association between polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, midtrimester vaginal microflora, vaginal interleukin receptor antagonist and interleukin-1beta levels and subsequent spontaneous preterm birth.
  
  
  METHODS
  Vaginal samples from 212 women, collected at 18-22 weeks' gestation, were analyzed for the polymorphism in intron 2 of the interleukin-1 receptor antagonist gene by polymerase chain reaction, qualitative and quantitative vaginal microflora, and interleukin-1beta and interleukin-1ra concentrations by enzyme-linked immunosorbent assay. Pregnancy outcome data were subsequently obtained.
  
  
  RESULTS
  Carriage of intron 2 of the interleukin-1 receptor antagonist allele 2 (IL1RN * 2) was associated with an elevated vaginal pH in black ( P < .001) and white ( P = .005) women, a reduced interleukin-1beta response to anaerobic Gram-negative rods and/or Gardnerella vaginalis ( P < .01), and a decreased rate of spontaneous preterm deliveries (6% versus 18%, P = .02). In black women, IL1RN * 2 carriage was associated with increased anaerobic Gram-negative rods, Mycoplasma, and Peptostreptococci and decreased Lactobacilli colonization.
  
  
  CONCLUSIONS
  IL1RN * 2 carriage was associated with a blunted proinflammatory interleukin-1beta response to abnormal vaginal flora. This property may decrease susceptibility to infection-related preterm birth.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Mehmet R
authors.initials: MR
authors.lastname: Genc
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Onderdonk
authors.forename: Santosh
authors.initials: S
authors.lastname: Vardhana
authors.forename: Mary L
authors.initials: ML
authors.lastname: Delaney
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Tuomala
authors.forename: Lilly-Rose
authors.initials: LR
authors.lastname: Paraskevas
authors.forename: Steven S
authors.initials: SS
authors.lastname: Witkin
mesh_terms: D000328:Adult; D001419:Bacteria / Q000302:isolation & purification; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007438:Introns / Q000235:genetics; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D047928:Premature Birth / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D012795:Sialoglycoproteins / Q000235:genetics*; D014621:Vagina / Q000378:metabolism / Q000382:microbiology; D016585:Vaginosis, Bacterial / Q000235:genetics*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins