712: Association Of Interleukin-1 and Interleukin-1 receptor antagonist (IL-1RN) gene expression with maternal and fetal IL-1RN genotype and chorioamnionitis in preterm birth

Abstract

1RN) GENE EXPRESSION WITH MATERNAL AND FETAL IL-1RN GENOTYPE AND CHORIOAMNIONITIS IN PRETERM BIRTH CHAD GROTEGUT, JENNA BONE, DAVID CROSSLIN, ELIZABETH HAUSER, BERNARD CANZONERI, GEETA SWAMY, PHILLIP HEINE, AMY MURTHA, Duke University, Obstetrics and Gynecology, Durham, North Carolina, Duke University, Center for Human Genetics, Durham, North Carolina OBJECTIVE: Inflammatory pathways play an important role in the pathogenesis of preterm delivery. Interleukin-1 is a potent pro-inflammatory cytokine where interleukin-1 receptor antagonist (IL-1RN) is an inhibitor of the IL-1 receptor, with anti-inflammatory properties. Maternal carriage of a polymorphism in the IL-1RN gene is associated with preterm delivery. We hypothesize that the presence of this polymorphism is associated with alterations in placental gene expression of IL-1 and/or IL-1RN. We sought to determine if gene expression of IL-1 and IL-1RN correlates with maternal and/or fetal IL-1RN genotype or with the incidence of chorioamnionitis in preterm subjects. STUDY DESIGN: Following IRB approval, we conducted a retrospective cohort study of subjects with spontaneous preterm delivery less than 37 weeks with placental samples available for quantitative gene expression analysis and maternal and fetal genotype for the IL-1RN polymorphism. Messenger RNA was extracted and quantitative real-time polymerase chain reaction performed for IL-1 and IL-1RN. The association of gene expression to maternal and fetal IL-1RN genotype and presence of chorioamnionitis was then determined by logistic regression. RESULTS: Gene expression data for IL-1 and IL-1RN was determined for 31 women delivering preterm. The data was similar when normalized to a housekeeping gene. There was a clear relationship between the incidence of chorioamnionitis and preterm delivery, especially in the setting of PPROM (OR 13.9, CI 2.5-118.0). There was no relationship between expression levels of IL-1 and IL1RN and maternal and fetal IL-1RN genotype (p 0.44 and p 0.67 respectively) or the presence of chorioamnionitis (p 0.36). CONCLUSION: We found no association between the placental gene expression of IL-1 and IL-1RN with maternal or fetal carraige of the IL-1RN polymorphism, nor with the presence of histologic chorioamnionitis. The balance between the pro-inflammatory IL-1 cytokine and the anti-inflammatory IN-1RN cytokine likely alone does not determine the presence of chorioamniontis.