SUMMARY
Objective. To evaluate changes in Toll-like receptor 4 (TLR4) expression and the methylation profile of the SIGIRR gene in preterm newborns with necrotizing enterocolitis (NEC), to examine their associations with gestational age and birth weight, and to assess their possible significance in NEC pathogenesis. Material and methods. The study was conducted at the Scientific Research Institute of Pediatrics named after K.Y. Farajova. Laboratory analyses were performed at the Human Genetics Laboratory and at the DIAGEN and INTERGEN laboratories in Ankara. TLR4 gene expression was assessed in 50 blood samples by real-time polymerase chain reaction. The methylation profile of the SIGIRR gene was analyzed in 52 blood samples across 36 gene loci. Participants were stratified by birth weight into groups below and above 1500 g, and children with NEC were compared with corresponding comparison groups. Between-group differences were assessed using the Mann–Whitney U test, and associations between variables were evaluated by Spearman rank correlation. A p value <0.05 was considered statistically significant. Results. TLR4 ΔΔCt correlated negatively with gestational age (ρ=-0.419; p=0.006) and birth weight (ρ=-0.424; p=0.006). In children weighing less than 1500 g, differences in methylation at the SIGIRR %C90, %C100, %C102, and %C258 loci were found compared with the comparison group. In children weighing more than 1500 g, changes at %C327 and %C123 were recorded. Several statistically significant correlations were also found between SIGIRR methylation indices and TLR4 parameters. Conclusion. NEC in preterm newborns is accompanied by changes in TLR4 expression and the methylation profile of the SIGIRR gene. Gestational age and birth weight were associated with TLR4 parameters. Associations between methylation changes at SIGIRR loci and TLR4 parameters suggest a possible interaction between these signaling mechanisms in NEC pathogenesis. Larger studies are needed to determine the early diagnostic and prognostic value of these markers.
Keywords: necrotizing enterocolitis, preterm newborn, TLR4, SIGIRR, gene expression

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