278. IGF2 polymorphisms predict pregnancy outcome

Abstract

IGF-II is an important determinant of placental trophoblast invasion and subsequent placental function. IGF-II can act in autocrine/paracrine and endocrine fashions to promote placental invasion and differentiation and within both the fetus and placenta to promote fetal growth. We aimed to determine whether polymorphisms in Igf2 are associated with common pregnancy complications associated with uteroplacental insufficiency. Pregnant women were recruited in early pregnancy for a prospective case control study at the Women's and Children's Hospital and Lyell McEwin Health Service, Adelaide, Australia. Buffy coats were retrieved from maternal blood sampled at 15 weeks gestation, paternal blood and cord blood collected following delivery. Pregnancy outcomes were classified into normal (n = 126), preeclampsia (PE, n = 31), gestational hypertension (GH, n = 18), small-for-gestational-age (SGA, n = 50), PE+SGA (n = 16) or preterm birth (PTB, n = 19) by an experienced obstetrician. Three polymorphisms in Igf2, Igf2 ApaI and Igf2 MspI single nucleotide polymorphisms, and INS+2336 deletion/insertion polymorphism were selected for investigation. DNA was extracted from buffy coats and genotyping was performed by PCR followed by High Resolution Melt analyses. Data were analysed by Chi Square and Fisher's Exact Test and Likelihood Ratios (LR) were calculated. In normal pregnancies, all polymorphisms were in Hardy–Weinberg Equilibrium. Igf2 ApaI in the neonate, and hence placenta, was associated with PE (P = 0.016, LR = 7.46) and PTB (P = 0.024, LR = 8.61). Neonatal Igf2 MspI was associated with SGA (P = 0.007, LR = 9.81). Gestational age was associated with maternal Igf2 ApaI (P = 0.0004) and INS+2336 (P = 0.0021), as well as neonatal INS+2336 (P = 0.0046). Birthweight was associated with paternal Igf2 MspI (P = 0.044) when corrected for gestational age. Although this work is ongoing, data thus far suggest polymorphisms in the gene encoding IGF-II, primarily in the placenta, are associated with a range of pregnancy complications which have been associated with impaired placental function. Ongoing research will determine whether these polymorphisms are associated with aberrant placental Igf2 expression.