441. Renin angiotensin system polymorphisms are associated with pregnancy complications

Abstract

Preeclampsia (PE), small for gestational age (SGA) and preterm birth (PTB) together affect 20% of first pregnancies. Currently there is no reliable way to identify women at risk. Polymorphims in genes in the renin angiotensin system (RAS) may be associated with impaired placentation and poor maternal response to pregnancy and hence predict risk for pregnancy complications. We aimed to determine if three functional polymorphisms in RAS genes, namely, AGT M235T, ACE (I/D) and AT1R A1166C are associated with pregnancy complications. Pregnancy trios were prospectively recruited from two public hospitals in Adelaide. Pregnancies were classified into normal (n = 110), PE (n = 26), SGA (n = 47), PE+SGA (n = 12), gestational hypertension (GH, n = 17), PTB (n = 20). PE, PE +SGA and GH were also grouped together as hypertension. Parental blood and maternal blood pressure was sampled or measured at 15 weeks gestation. Cord blood was sampled after delivery. DNA was extracted from buffy coats and genotyped using high resolution melt analyses. Maternal plasma [ACE] was measured by ELISA. Data were analysed by ANOVA and Fisher's exact test. Likelihood ratios (LR) were calculated where appropriate. Maternal ACE I/D was associated with hypertension (P = 0.001, LR = 14.8) and SGA (P = 0.019, LR = 10). Paternal AT1R A1166C was associated with PTB (P = 0.01, LR = 7.4). For ACE I/D, plasma [ACE] in women with DD was 33% and 62% higher than ID and II, respectively (both P < 0.001). Systolic blood pressure in women with DD was 6% higher than II (P = 0.04). Our data suggest that RAS polymorphisms are associated with pregnancy complications. Furthermore, maternal ACE genotype determines plasma [ACE] and affects blood pressure at 15 weeks gestation, well before symptoms manifest. Our data also suggest that paternal genotype may be important in determining risk for pregnancy complications, consistent with the role of paternity in their aetiology.