526. GENETIC POLYMORPHISMS IN INTERLEUKIN-1 FAMILY MEMBERS AND PREGNANCY OUTCOME

Abstract

Poor placental development is associated with a variety of common, potentially life-threatening pregnancy complications, including preeclampsia (PE) and small-for-gestational-age (SGA) babies. The placenta and fetus express a combination of maternal and paternal genes. Interleukin-1 alpha (IL-1α) and -1 beta (IL-1β) promote trophoblast invasion by upregulating expression of matrix metalloproteinases, while interleukin-1 receptor antagonist (IL-1RN) acts as a competitive inhibitor of IL-1 a and IL-1β by binding to the IL-1 receptor. We hypothesis that polymorphisms which decrease IL-1 activity, within IL-1α rs1800587 (C-allele) and rs17561 (T-allele), IL-1β rs16944 (C-allele) and IL-1RN rs454078 (A-allele) affect placental development and thus pregnancy outcome. To determine the effect of the IL-1 SNPs on pregnancy outcome, blood was collected prospectively from pregnant women at 15 weeks gestation and from their partners and babies at birth. DNA was extracted and genotyped by Sequenom MassArray. Pregnancies were fully characterised and classified into control or PE, PE+SGA, SGA after delivery by an experienced obstetrician. The IL-1α rs1800587 fetal genotype was associated with PE+SGA and smaller head circumference at birth. IL-1α rs17561 fetal genotype was associated with PE+SGA, and a smaller head circumference and body length at birth. The frequency of IL-1β C-allele was associated with PE in neonates, and in fathers the CC homozygote genotype was associated with decreased placental weight at birth. The IL-1RN rs454078 maternal genotype was associated with PE and maternal waist circumference while fetal AA genotype was associated with SGA and decreased placental weight at birth. Genotypes which decrease the production of IL-1α and IL-1β while increasing IL-1RN will reduce proinflammatory cytokines and thereby affect the invasive potential of placental trophoblasts. We have shown that these polymorphisms in both parents may be associated with poor pregnancy outcome. Suggesting that both partners contribute to placental differentiation and function.