INFLUENCE OF ANGIOTENSIN CONVERTING ENZYME GENE POLYMORPHISM ON PREGNANCY OUTCOME IN WOMEN WITH HISTORY OF PRE-ECLAMPSIA

Abstract

Background: Women who have had pre-eclampsia (PE) are more prone to recurrent negative pregnancy outcomes and altered utero-placental and umbilical flows in their future pregnancy. In addition, to an increased risk of later cardiovascular diseases, which clearly suggest a shared aetiology. Yet, the mechanisms involved have not been identified. Although, the causes of PE are not well understood, there is a possibility that PE has, at least in part, a genetic basis. The physiological remodelling of spiral arteries throughout pregnancy is mediated by the rennin-angiotensin system (RAS). The ACE I/D polymorphism of the ACE gene accounted for 47% of total phenotypic variance of the serum Angiotensin converting enzyme (ACE), contributing much to the variability of the ACE level. Previous studies failed to reproduce a persistent link of ACE I/D genotype and PE in nulliparous women. Objective: In this prospective study, we analysed the association of the ACE genotype and the recurrence of PE and/or fetal growth restriction (FGR) in subsequent pregnancy in women at high risk for a previous PE as primipara, without other known risk conditions. Patients and Methods: Sixty women with history of PE as primipara, with no known risk factors apart from nulliparity, were recruited in their second pregnancy. Their ACE genotyping were detected. Uterine arteries resistance indices (RI) and umbilical artery pulsatility index (PI), were recorded at 16th, 20th, 24th weeks of gestation and clinical pregnancy outcome was analyzed, as well. Results: ACE I/D genotype distribution among our cases of 90 Egyptian pregnant women were compatible to other races in literature. DD genotype was detected in 41.1% of our cases, 34.4% were ID genotype and 24.4% were II genotype. Significant difference in ACE I/D genotype and D-allele frequency were observed in cases with recurrent PE and/or FGR. Mid trimester uterine arteries resistance indices (RI) at 16th, 20th, 24th weeks of gestation, and umbilical artery pulsatility index (PI) at 20th, 24th weeks were significantly higher in DD genotype group compared to ID and II genotype respectively. In addition, DD genotype group had significantly lower gestational age at time of delivery, lower birth weight and placental weight. Conclusion: ACE DD genotype and D- allele frequency adversely affected pregnancy outcome and utero-placental and umbilical flow velocimetry in women with history of preeclampsia as nulliparous without known risk factors apart from nulliparity.