Polymorphism of antioxidant defense genes as a predictor of unfavorable neurological outcomes in preterm children

Abstract

   Currently, oxidative stress is considered as one of the most important factors in the pathogenesis of many pathological processes occurring in the newborn baby.   Purpose. To establish the relationship of the polymorphism of genes, encoding antioxidant enzymes (glutamyl cysteine ligase, manganine superoxide dismutase) with unfavorable neurological outcomes in preterm children at various age periods.   Material and methods. A prospective cohort continuous study included 151 preterm children, with a gestational age of 26–32 weeks and body weight of 590–1990 grams. Cord blood was sampled in children to determine allelic polymorphisms of 4 genetic markers: the SOD2 gene rs4880 (с.47C>Т, р.Ala16Val), the SOD2 gene rs1141718 (с.58T>C, р.Thr58Ile), the SOD2 gene rs11575993 (с.60С>Т, р.Leu58Phe), GCLC gene rs17883901 (с.–129 С>Т). The division of children into groups was carried out based on the assessment of neurological outcomes at the following control points: 1 control point — at the time of discharge from hospital, 2 control point — corrected age of 1 year of life, 3 control point — 4 years of life.   Results. The cohort of children with unfavorable neurological outcomes was found to increase from 36.4 % at the time of hospital discharge to 70 % by the age of 4 years. Children who joined the cohort of children with unfavorable neurological outcomes at corrected age of 1 year of life were carriers of 47 CT of the gene of the mitochondrial superoxide dismutase (SOD2) rs4880, and those, attached by 4 years of age, were carriers of heterozygous 129 CT genotype of the gene of the catalytic subunit of glutamate cysteine ligase (GCLC) rs17883901 and 47 CT mitochondrial superoxide dismutase (SOD2) rs4880. Children with a favorable neurological outcome at corrected age of 1 year of life were more often diagnosed with homozygous 47 CC genotype of SOD2 rs4880 and 60 CC SOD2 rs11575993, and at the age of 4 years of life — with homozygous 129 CC genotype of GCLC rs17883901 gene and 47 TTSOD2 rs4880.   Conclusion. The study of single nucleotide exchange in the antioxidant enzyme genes will establish the risk group of children exposed to free-radical injuries of CNS and begin neuroprotective therapy with the inclusion of antioxidant treatment.