title: Is the C242T Polymorphism of the CYBA Gene Linked with Oxidative Stress-Associated Complications of Prematurity?
abstract: The C242T polymorphism of CYBA (cytochrome B-245 alpha chain), the gene encoding the p22phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, has been linked to several conditions in which oxidative stress plays a pathogenic role. We investigated in a cohort of 451 preterm infants [gestational age (GA) ≤30 weeks] the association of the polymorphism with the risk of developing neonatal respiratory distress syndrome (RDS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, patent ductus arteriosus, or intraventricular hemorrhage. We observed a significant association of the TT/CT genotype with RDS [odds ratio (OR) 2.34, 95% confidence interval (95% CI) 1.28-3.90], ROP (OR 1.72, 95% CI 1.05-2.80), and BPD (OR 1.60, 95% CI 1.05-2.43). When this dominant model was adjusted to account for GA, birth weight, and sex, it remained significant for the three outcomes. This study is the first to address the association of a polymorphism related to the NADPH family with oxidative stress-related complications of prematurity. Since p22phox is essential for reactive oxygen species production by NADPH oxidase, we hypothesize that genetic variations in the protein may lead to differences in susceptibility to oxidative stress-induced damage in preterm infants. Antioxid. Redox Signal. 27, 1432-1438.
authors.affiliation: 1 Department of Pediatrics, Maastricht University Medical Center (MUMC+) , School for Oncology and Developmental Biology (GROW), Maastricht, The Netherlands .
authors.forename: Maurice J
authors.initials: MJ
authors.lastname: Huizing
authors.affiliation: 2 Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan, Italy .
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cavallaro
authors.affiliation: 3 Department of Pediatrics, Zuyderland Medical Center Heerlen , Heerlen, The Netherlands .
authors.forename: Rob M
authors.initials: RM
authors.lastname: Moonen
authors.affiliation: 4 Department of Pediatrics, Hospital Universitario Materno-Infantil de Canarias , Las Palmas de Gran Canaria, Spain .
authors.forename: Gema E
authors.initials: GE
authors.lastname: González-Luis
authors.affiliation: 2 Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano , Milan, Italy .
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.affiliation: 5 Department of Neonatology, University and Polytechnic Hospital La Fe , Valencia, Spain .
authors.forename: Máximo
authors.initials: M
authors.lastname: Vento
authors.affiliation: 1 Department of Pediatrics, Maastricht University Medical Center (MUMC+) , School for Oncology and Developmental Biology (GROW), Maastricht, The Netherlands .
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villamor
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000235:genetics; D003596:Cytosine / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000235:genetics*; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics; D012178:Retinopathy of Prematurity / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
chemical_list: D014443:Tyrosine; D003596:Cytosine; D019255:NADPH Oxidases; C086986:CYBA protein, human
keywords: NADPH oxidase; oxidative stress; p22phox; polymorphisms; preterm infant; retinopathy of prematurity