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

Ewa Strauss; Anna Gotz-Więckowska; Alicja Sobaniec; Anna Chmielarz-Czarnocińska; Dawid Szpecht; Danuta Januszkiewicz-Lewandowska

doi:10.3390/genes14050975

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

Genes (Basel). 2023 Apr 26;14(5):975. doi: 10.3390/genes14050975.

Authors

Ewa Strauss¹, Anna Gotz-Więckowska², Alicja Sobaniec³, Anna Chmielarz-Czarnocińska², Dawid Szpecht³, Danuta Januszkiewicz-Lewandowska^{4

5}

Affiliations

¹ Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland.
² Department of Ophthalmology, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569 Poznan, Poland.
³ Department of Neonatology, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland.
⁴ Department of Medical Diagnostics, Poznan University of Medical Sciences, Dobra Street 38a, 60-595 Poznan, Poland.
⁵ Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.

Abstract

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.

Keywords: HIF1A gene; VEGFA gene; hypoxia; hypoxia at birth; prematurity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Female
Humans
Hypoxia / genetics
Infant, Newborn
Infant, Newborn, Diseases*
Parturition
Polymorphism, Single Nucleotide*
Pregnancy
Risk Factors

Grants and funding

The work has been supported by the Scientific Research Committee in Poland under grant no. 2 P05E 098 30 (A.G.-W. and E.S.) and the Poznan University of Medical Sciences research grant for young employees (up to 35 years of age) and participants of four-year doctoral studies in 2018, no. 502-14-11121500-41229 (A.C.-C. and E.S.).