Polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, local midtrimester cytokine response to vaginal flora, and subsequent preterm birth.
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.
Genc
Mehmet R
MR
Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Onderdonk
Andrew B
AB
Vardhana
Santosh
S
Delaney
Mary L
ML
Norwitz
Errol R
ER
Tuomala
Ruth E
RE
Paraskevas
Lilly-Rose
LR
Witkin
Steven S
SS
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*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins