title: Association of NOS3 tag polymorphisms with hypoxic-ischemic encephalopathy.
abstract: OBJECTIVE
  To test the association of NOS3 gene with hypoxic-ischemic encephalopathy (HIE).
  
  
  METHODS
  The study included 110 unrelated term or preterm born children (69 boys and 41 girls) with HIE and 128 term and preterm born children (60 boys and 68 girls) without any neurological problems after the second year of life. Children with perinatal HIE fulfilled the diagnostic criteria for perinatal asphyxia. All children were admitted to the Clinical Hospital Split between 1992 and 2008. We analyzed 6 tagging single nucleotide polymorphisms (SNP) within NOS3 gene (rs3918186, rs3918188, rs1800783, rs1808593, rs3918227, rs1799983), in addition to previously confirmed NOS3-associated SNP rs1800779. Genotyping was conducted using real-time polymerase chain reaction (PCR). Association analyses were performed according to allelic and genotypic distribution.
  
  
  RESULTS
  Allelic test did not show any SNP association with HIE. SNP rs1808593 showed genotype association (P=0.008) and rs1800783-rs1800779 TG haplotype showed an association with HIE (P<0.001). The study had 80% statistical power to detect (α=0.05) an effect with odds ratio (OR)=2.07 for rs3918186, OR=1.69 for rs3918188, OR=1.70 for rs1800783, OR=1.80 for rs1808593, OR=2.10 for rs3918227, OR=1.68 for rs1800779, and OR=1.76 for rs1799983, assuming an additive model.
  
  
  CONCLUSIONS
  Despite the limited number of HIE patients, we observed genotypic and haplotype associations of NOS3 polymorphisms with HIE.
authors.affiliation: Department of Pediatrics, Clinical Hospital Centre Split, Split, Croatia.
authors.forename: Radenka
authors.initials: R
authors.lastname: Kuzmanić Samija
authors.forename: Dragan
authors.initials: D
authors.lastname: Primorac
authors.forename: Biserka
authors.initials: B
authors.lastname: Resić
authors.forename: Bernarda
authors.initials: B
authors.lastname: Lozić
authors.forename: Vjekoslav
authors.initials: V
authors.lastname: Krzelj
authors.forename: Maja
authors.initials: M
authors.lastname: Tomasović
authors.forename: Eugenio
authors.initials: E
authors.lastname: Stoini
authors.forename: Ljubo
authors.initials: L
authors.lastname: Samanović
authors.forename: Benjamin
authors.initials: B
authors.lastname: Benzon
authors.forename: Marina
authors.initials: M
authors.lastname: Pehlić
authors.forename: Vesna
authors.initials: V
authors.lastname: Boraska
authors.forename: Tatijana
authors.initials: T
authors.lastname: Zemunik
mesh_terms: D000465:Algorithms; D001034:Apgar Score; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis / Q000235:genetics*; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013223:Statistics as Topic
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III