Influence of functional variations in genes of neurotrophins and neurotransmitter systems on the development of retinopathy of prematurity

Fevereiro-Martins, Mariza; Santos, Ana Carolina; Marques-Neves, Carlos; Guimarães, Hercília; Bicho, Manuel

http://hdl.handle.net/10400.5/98427

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Authors

Fevereiro-Martins, Mariza

Santos, Ana Carolina

Marques-Neves, Carlos

Guimarães, Hercília

Bicho, Manuel

Abstract(s)

Retinal neurodevelopment, vascularization, homeostasis, and stress response are influenced by factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and erythropoietin (EPO). As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age < 32 weeks or birth weight < 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY® platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers.

Description

© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Keywords

Angiogenesis Brain-derived neurotrophic factor Erythropoietin Gene expression Nerve growth factor Neurotrophic factors Oxidative stress Retinal vascular disease Retinopathy of prematurity Tyrosine hydroxylase