Genetic Contributions to the Development of Complications in Preterm Newborns.

Chiara Poggi,Elena Gozzini,Ilaria Romagnuolo,Alice Sereni,Elisabetta Pasquini,Rosanna Abbate,Betti Giusti,Carlo Dani,Ada Kura,Lynette K Rogers

doi:10.1371/journal.pone.0131741

Abstract

AimWe aimed to identify specific polymorphisms of genes encoding for vascular endothelial growth factor A (VEGFA), endothelial nitric oxide synthase (eNOS), renin-angiotensin system (angiotensinogen gene [AGT], angiotensinogen type 1 receptor [AGTR1], angiotensin-converting enzyme [ACE]), and heme oxygenase-1 (HMOX-1) in a cohort of preterm infants and correlate their presence with the development of respiratory distress syndrome (RDS) requiring mechanical ventilation (MV), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP).Study DesignWe carried out a retrospective study to evaluate the allele frequency and genotype distribution of polymorphisms of VEGFA, eNOS, AGT, AGTR1, ACE, and HMOX-1 in a population of preterm neonates (n=342) with a gestational age ≤28 weeks according to the presence or absence of RDS requiring MV, BPD, IVH, or ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP.ResultsIn our population 157 infants developed RDS requiring MV, 71 BPD, 70 IVH, and 43 ROP. We found that TC+CC rs2070744 eNOS (41.7 vs. 25.4%, p=0.01) and GT+TT rs1799983 eNOS (51.8 vs. 35.2%, p=0.01) polymorphisms are independent risk factors for BPD. Haplotype reconstruction showed that haplotypes in VEGF and eNOS are significantly associated with different effects on RDS, BPD, IVH, and ROP in our population.ConclusionsWe found that TC+CC rs2070744 eNOS and GT+TT rs1799983 eNOS polymorphisms are independent predictors of an increased risk of developing BPD. Haplotypes of VEGFA and eNOS may be independent protective or risk markers for prematurity complications.

Highlights

There is increasing evidence that some genepolymorphismsare implicated in the development of severe complications of preterm birth, including respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP).Vascular endothelial growth factor A (VEGFA) is important for the physiological growth of retinal vessels, and experimental and clinical data suggest that VEGF may play a causative role in the development of ROP [1]
We found that TC+CC rs2070744 endothelial Nitric oxide (NO) synthase (eNOS) (41.7 vs. 25.4%, p=0.01) and GT+TT rs1799983 eNOS (51.8 vs. 35.2%, p=0.01) polymorphisms are independent risk factors for BPD
Haplotype reconstruction showed that haplotypes in VEGF and eNOS are significantly associated with different effects on RDS, BPD, IVH, and ROP in our population

Summary

Introduction

Vascular endothelial growth factor A (VEGFA) is important for the physiological growth of retinal vessels, and experimental and clinical data suggest that VEGF may play a causative role in the development of ROP [1]. Clinical studies suggest a relevant association between VEGFA activity and BPD development in preterm infants [3,4]. Nitric oxide (NO) has several vascular actions which may contribute to the growth and protection of vessels in preterm infants [5]. This seems to be confirmed by the reported association between endothelial NO synthase (eNOS) gene activity and the risk of developing RDS, BPD, and IVH in this population [6]

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