title: Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy.
abstract: The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.
authors.affiliation: Department of Pediatrics, University Hospital Split, Split, Croatia.
authors.forename: R
authors.initials: R
authors.lastname: Kuzmanić Šamija
authors.affiliation: School of Medicine Split, University of Split, Split, Croatia.
authors.forename: D
authors.initials: D
authors.lastname: Primorac
authors.affiliation: School of Medicine Split, University of Split, Split, Croatia.
authors.forename: B
authors.initials: B
authors.lastname: Rešić
authors.affiliation: Department of Neonatology, University Hospital Split, Split, Croatia.
authors.forename: V
authors.initials: V
authors.lastname: Pavlov
authors.affiliation: Department of Nuclear Medicine, University Hospital Split, Split, Croatia.
authors.forename: V
authors.initials: V
authors.lastname: Čapkun
authors.affiliation: School of Medicine Split, University of Split, Split, Croatia.
authors.forename: H
authors.initials: H
authors.lastname: Punda
authors.affiliation: Department of Pediatrics, University Hospital Split, Split, Croatia.
authors.forename: B
authors.initials: B
authors.lastname: Lozić
authors.affiliation: Department of Medical Biology, School of Medicine Split, University of Split, Split, Croatia.
authors.forename: T
authors.initials: T
authors.lastname: Zemunik
mesh_terms: D001724:Birth Weight; D001925:Brain Damage, Chronic / Q000235:genetics*; D016009:Chi-Square Distribution; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics* / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III