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Am J Obstet Gynecol. 2003 Nov;189(5):1413-7.

Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype influences midtrimester amniotic fluid concentrations of interleukin-1beta and interleukin-1 receptor antagonist and pregnancy outcome.

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Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, 525 E. 68th Street, Box 35, New York, NY 10021, USA.



Preterm labor in experimental models is initiated by intra-amniotic interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated with variations in IL-1beta and IL-1ra production. The relationship among the IL-1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second-trimester amniotic fluid, and pregnancy outcome was determined.


Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction. Pregnancy outcomes were obtained after completion of testing.


The distribution of fetal IL-1ra genotypes was similar to that found in other populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes, whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2 was associated with a greater than 50% increase in midtrimester intra-amniotic IL-1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2 homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra, was related to an increased rate of preterm birth (P<.0001). In the 11 pregnancies that were subsequently terminated because of major malformations, there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was unrelated to IL-1ra genotype.


Possession by the fetus of the IL1RN*2 allele is associated with enhanced intraamniotic IL-1beta production. Induction of an intra-amniotic proinflammatory immune response might be more likely to lead to preterm labor in fetuses carrying the IL1RN*2 allele.

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