SELENOP rs3877899 Variant Affects the Risk of Developing Advanced Stages of Retinopathy of Prematurity (ROP).

The significance of selenoproteins for the incidence of prematurity and oxidative-damage-related diseases in premature newborns is poorly understood. The latter are at risk for ROP as well as BPD, IVH, PDA, RDS, and NEC, which is particularly high for newborns with extremely low gestational age (ELGA) and extremely low birth weight (ELBW). This study evaluates the hypothesis that variation in the selenoprotein-encoding genes SELENOP, SELENOS, and GPX4 affects the risk of ROP and other comorbidities. The study included infants born ≤ 32 GA, matched for onset and progression of ROP into three groups: no ROP, spontaneously remitting ROP, and ROP requiring treatment. SNPs were determined with predesigned TaqMan SNP genotyping assays. We found the association of the SELENOP rs3877899A allele with ELGA (defined as <28 GA), ROP requiring treatment, and ROP not responsive to treatment. The number of RBC transfusions, ELGA, surfactant treatment, and coexistence of the rs3877899A allele with ELGA were independent predictors of ROP onset and progression, accounting for 43.1% of the risk variation. In conclusion, the SELENOP rs3877899A allele associated with reduced selenium bioavailability may contribute to the risk of ROP and visual impairment in extremely preterm infants.

Hypoxia-Inducible Pathway Polymorphisms and Their Role in the Complications of Prematurity.

Excessive oxidative stress resulting from hyperoxia or hypoxia is a recognized risk factor for diseases of prematurity. However, the role of the hypoxia-related pathway in the development of these diseases has not been well studied. Therefore, this study aimed to investigate the association between four functional single nucleotide polymorphisms (SNPs) in the hypoxia-related pathway, and the development of complications of prematurity in relation to perinatal hypoxia. A total of 334 newborns born before or on the 32nd week of gestation were included in the study. The SNPs studied were HIF1A rs11549465 and rs11549467, VEGFA rs2010963, and rs833061. The findings suggest that the HIF1A rs11549465T allele is an independent protective factor against necrotizing enterocolitis (NEC), but may increase the risk of diffuse white matter injury (DWMI) in newborns exposed to hypoxia at birth and long-term oxygen supplementation. In addition, the rs11549467A allele was found to be an independent protective factor against respiratory distress syndrome (RDS). No significant associations with VEGFA SNPs were observed. These findings indicate the potential involvement of the hypoxia-inducible pathway in the pathogenesis of complications of prematurity. Studies with larger sample sizes are needed to confirm these results and explore their clinical implications.