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

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.

Role of Fibronectin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants

“…From our previous studies, we were able to highlight the significance of methylenetetrahydrofolate reductase (MTHFR 1298A > C) polymorphism as a possible risk factor for IVH due to increased levels of plasma homocysteine [35]. Similarly, there was approximately a 3.5-fold increased risk of developing IVH in preterm infants with the GT eNOS 894G > T polymorphism of endothelial nitric oxide synthase (eNOS), a gene associated with blood flow [12]. Prasun P et al examined polymorphisms in VEGF and showed a higher prevalence of IVH in infants with GA/AA and AA/AC genotypes in VEGF RS1570360 and VEGF RS699947, respectively [36].…”

“…Analysis of the role of genetic factors in the pathophysiology of IVH will make it possible to determine the group of newborns who are specifically at risk of developing IVH in the perinatal period. The following genetic factors that may predispose to IVH have been analyzed so far: polymorphisms of genes coding for proinflammatory cytokines [7,8], coagulation pathway [9][10][11] regulation of systemic blood pressure and cerebral blood flows [12], as well as structural components of the germinal matrix [13,14]. There is still not enough definitive information about the connection between the increased risk of IVH and the molecular structure of the vasculature in the germinal matrix.…”

Association between Lys198Asn polymorphism of endothelin‐1 gene and ischemic stroke: A meta‐analysis

“…shown an independent association of Lys198Asn SNP of the EDN1 gene and number of diseases such as hypertension (Barath et al, 2007;Barbeau et al, 2003;Fang, Li, & Ma, 2017;Jin et al, 2003), obesity (Karita & Sadewa, 2019) (Colombo, Ciofini, Paradossi, Bevilacqua, & Biagini, 2006), diabetes (Li et al, 2008), pulmonary hypertension (Benza et al, 2015), intraventricular hemorrhage (SzpechtOctober , Gadzinowski, Seremak-Mrozikiewicz, Kurzawińska, & Szymankiewicz, 2016), and subarachnoid hemorrhage (Foreman et al, 2017;Gallek et al, 2013). Therefore, the Lys198Asn SNP is considered to be a risk factor for cardiovascular disease and cerebrovascular disease.…”

Genetic drivers of cerebral blood flow dysfunction in TBI: a speculative synthesis

“…Furthermore, NOS3 displays close association with endothelin function, as exemplified in the development of preterm infant intraventricular haemorrhage (via the association of NOS3 and endothelin-1 polymorphisms). 54 Dysfunctional NOS activity can lead to the development or potentiation of pathological states. A variety of SNPs in genes that regulate NOS and other downstream mediators in the nitric oxide pathway have been linked to vascular pathology.…”