114. HYPERTENSIVE DISORDERS OF PREGNANCY ARE ASSOCIATED WITH IMMUNOREGULATORY GENE POLYMORPHISMS

Abstract

Pregnancy is a controlled state of inflammation. Deregulation of cytokine networks can lead to adverse pregnancy outcomes including preeclampsia (PE). We aimed to identify single nucleotide polymorphisms in immunoregulatory genes that signify an increased risk of the gestational hypertensive disorders PE and gestational hypertension (GH). 1169 nulliparous pregnant women and their partners were recruited prospectively for the Adelaide SCOPE study. PE and GH were classified using strict guidelines. Uncomplicated pregnancies served as controls. Peripheral blood from couples and cord blood from neonates were collected. DNA was extracted and genotyped for Interleukin (IL)-6 rs1800795, IL-4 rs2243250, IL-10 rs1800896 and rs1800871, mannose binding lectin (MBL) rs1800450, transforming growth factor beta 1 (TGFβ-1) rs1800469 and cyclooxygenase (COX)-2 rs20417 & rs5275 and inducible nitric oxide synthase (NOS2A) rs1137933 using the Sequenom MassARRAY system. Genotypes for Caucasian PE (n = 75) and GH (n = 102) were compared with controls (n = 422) and analysed using Chi-Square. In neonates IL-6 G allele carriage was associated with PE (P = 0.011, OR=2.0, 95% CI = 1.2–3.7) and the CC genotype associated with GH (P = 0.002). Neonatal IL-10 RS180071 AA genotype associated with PE (P = 0.041) and IL-10 RS1800896 AA associated with GH (P = 0.022). Paternal NOS2A C allele was more frequent in PE (P = 0.03, OR = 2.1, 95% CI = 1.1–4.5), and maternal NOS2A CC more frequent in GH (P = 0.018). Increased neonatal carriage of MBL rs1800450 AA+GA genotypes associated with GH (P = 0.03, OR = 2.2, 95% CI = 1.1–4.5). No associations were observed between TGFβ-1 or COX2 genotypes and PE or GH. Associations between neonatal IL-6 G, which confers high placental IL-6 expression, and PE suggest a possible mechanism by which PE is a pro-inflammatory exacerbation of placental origin. Since placental IL-10 is important for maternal tolerance of the fetus, genotypes predisposing to low IL-10 expression in the neonate which associate with both PE and GH, suggest a role for decreased placental IL-10 in these disorders.