engleski

Association of NOS3 tag polymorphisms with hypoxic-ischemic encephalopathy

Perinatal hypoxic-ischemic encephalopathy (HIE) is characterized with impaired cerebral circulation and increased activity of nitric oxide synthase (NOS). Activation of the NOS3 in endothelial cells has a neuroprotective role. Aim of this study was to test the association of NOS3 gene with HIE. 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 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 SNPs 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. Association analyses were performed under the additive and genotypic model. Allelic test did not observe any SNP association with HIE. Genotypic test detected association of rs1808593 with HIE (P=0.008). We also observed rs1800783-rs1800779 TG haplotype association with HIE (P<0.001). Our study had 80% statistical power to detect (at α=0.05) an effect of [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, [OR]=1.76 for rs1799983, assuming an additive model. Despite the limited number of HIE patients, we observed genotypic and haplotype associations of NOS3 polymorphisms with HIE.

infants; endothelial nitric oxide synthase (NOS3); hypoxic-ischemic encephalopathy; nitric oxide; tagging polymorphisms

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