Role of endothelial nitric oxide synthase and endothelin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants

Marta Szymankiewicz,Dawid Szpecht,Janusz Gadzinowski,Agnieszka Seremak-Mrozikiewicz,Grażyna Kurzawińska

doi:10.1038/srep42541

Abstract

In the pathogenesis of neonatal intraventricular hemorrhage (IVH) in preterm infants, an important role is played by changes in venous and arterial cerebral flows. It has been shown that the ability of autoregulation of cerebral flows in response to variations in arterial blood pressure in preterm infants is impaired. This impaired autoregulation causes an increased risk of germinal matrix rupture and IVH occurrence. We examined three polymorphisms of genes, related to regulation of blood flow, for an association with IVH in 100 preterm infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. These polymorphisms include: eNOS (894G > T and −786T > C) and EDN1 (5665G > T ) gene. We found that infants with genotype GT eNOS 894G > T have 3.4-fold higher risk developing of IVH born before 28 + 6 weeks of gestation. Our investigation did not confirm any significant prevalence for IVH development according to eNOS −786T > C genes polymorphism. Our novel investigations in EDN1 5665G > T polymorphism did not show any link between alleles or genotypes and IVH. Future investigations of polymorphisms in blood-flow associated genes may provide valuable insight into the pathogenetic mechanisms underlying the development of IVH.

Highlights

In the pathogenesis of neonatal intraventricular hemorrhage (IVH) in preterm infants, an important role is played by changes in venous and arterial cerebral flows
The infants were diagnosed according to grades of IVH; 15 (33.33%) newborns were diagnosed with IVH grade I, 20 (42.22%) with grade II, 8 (17.77%) with grade III and 3 (6.66%) with grade IV IVH
The incidence of IVH grade II to IV was: the higher the lower the gestational age and was significantly higher in children born from 24 + 0 to + 6 weeks of gestation than born from + 0 to 32 + 0 weeks of gestation (74.19% vs 25.81%); p = 0.007); the higher the lower Apgar score in first (6(1–10) vs 8(2–10); p = 0.007) and fifth minute of life (4(1–10) vs 7(1–8); p = 0.001); more often in children diagnosed with intrauterine infection (70.97% vs 47.83%; p = 0.031)

Summary

Introduction

In the pathogenesis of neonatal intraventricular hemorrhage (IVH) in preterm infants, an important role is played by changes in venous and arterial cerebral flows. NO and EDN1 physiologically interact to regulate vascular tone inseparably It seems that eNOS gene polymorphisms (894G >T or −786T >C) may increase the risk of IVH in preterm infants by significantly disrupting the regulation of cerebral flow[4,5]. While their impact on the development hemodynamic disturbances in newborns and IVH is unknown, research to date has shown that the polymorphic variant of the EDN1 gene: Lys198Asn plays a significant role in the pregnancy and in the pathogenesis of arterial hypertension in adults

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