Genetic Contributions to the Development of Complications in Preterm Newborns

• Published in: PloS one Vol. 10; no. 7; p. e0131741
• Main Authors: Poggi, Chiara, Giusti, Betti, Gozzini, Elena, Sereni, Alice, Romagnuolo, Ilaria, Kura, Ada, Pasquini, Elisabetta, Abbate, Rosanna, Dani, Carlo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14-07-2015; Public Library of Science (PLoS)
• Subjects: Angiotensin; Angiotensinogen; Angiotensinogen - genetics; Babies; Bronchopulmonary Dysplasia - complications; Cardiovascular disease; Clinical medicine; Cohort Studies; Complications; Congenital diseases; Deoxyribonucleic acid; DNA; Dysplasia; Enzymes; Female; Gene Frequency; Genes; Genotype; Genotypes; Gestational age; Haplotypes; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - genetics; Hemorrhage; Hospitals; Humans; Infant, Newborn; Infants; Intracranial Hemorrhages - complications; Lung diseases; Male; Mechanical ventilation; Medicine; Neonates; Newborn babies; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric-oxide synthase; Oxygenase; Pathogenesis; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Physiology; Polymorphism, Single Nucleotide; Pregnancy; Premature birth; Premature Birth - enzymology; Premature Birth - genetics; Premature Birth - therapy; Receptor, Angiotensin, Type 1 - genetics; Reconstruction; Renin; Respiration, Artificial; Respiratory distress syndrome; Respiratory Distress Syndrome, Newborn - complications; Retinopathy; Retinopathy of Prematurity - complications; Retrospective Studies; Risk analysis; Risk factors; Rodents; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Ventilation; Ventilators
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131741

We 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).
We 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.
In 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.
We 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.