Fetal interleukin-1 receptor antagonist gene polymorphism, intra-amniotic interleukin-1beta levels, and history of spontaneous abortion.
OBJECTIVE
The purpose of this study was to determine whether fetal carriage of specific alleles of the polymorphic interleukin-1 receptor antagonist gene is associated with variations in intra-amniotic cytokine levels and previous pregnancy outcomes.


METHODS
Fetal cells in midtrimester amniotic fluid from 189 women were tested for interleukin-1 receptor antagonist intron 2 length polymorphisms. Concentrations of cytokines in amniotic fluid were tested by enzyme-linked immunosorbent assay. Pregnancy history data were obtained subsequently.


RESULTS
Homozygosity for interleukin-1 receptor antagonist allele 1 was detected in 13 of 17 fetuses (76.5%) from women whose previous pregnancies all ended in spontaneous abortions, as compared with 33 of 74 fetuses (44.6%) from women with at least 1 previous term birth ( P = .02). Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with only 1 (5.9%) previous spontaneous abortion, as opposed to 31 pregnancies (41.9%) that were associated with a previous term delivery ( P = .004). A similar relationship between interleukin-1 receptor antagonist allele 1 and spontaneous abortions was observed when pregnancies of white women only were analyzed. Median mid trimester amniotic fluid interleukin-1beta concentrations were higher in women whose previous pregnancies ended in term deliveries (15.7 pg/mL), as opposed to women with 1 to 2 (6.4 pg/mL; P = .04) or > or =3 (4.1 pg/mL; P = .007) previous spontaneous abortions. Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with elevated intra-amniotic interleukin-1beta levels (16.2 pg/mL), as compared with interleukin-1 receptor antagonist allele 1 homozygotes (10.8 pg/mL; P = .03).


CONCLUSIONS
Fetal carriage of interleukin-1 receptor antagonist allele 1 is associated with reduced intra-amniotic interleukin-1beta concentrations and an increased occurrence of spontaneous abortions in previous pregnancies.
Perni
Sriram C
SC
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. scperni@yahoo.com
Vardhana
Santosh
S
Tuttle
Sara L
SL
Kalish
Robin B
RB
Chasen
Stephen T
ST
Witkin
Steven S
SS
D000022:Abortion, Spontaneous / Q000235:genetics*; D000653:Amniotic Fluid / Q000737:chemistry*; D005260:Female; D005333:Fetus / Q000502:physiology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis*; D007378:Interleukins / Q000032:analysis; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D047928:Premature Birth / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007378:Interleukins; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins