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Background : Necrotizing enterocolitis (NEC) is a common gastrointestinal emergency among neonates which is characterized by acute intestinal inflammation and necrosis. The main risk factors for NEC are prematurity, low birth weight, and some preexisting health conditions such as congenital heart defects (CHDs). Investigation of the potential genetic predisposition to NEC is a promising approach that might provide new insights into its pathogenesis. One of the most important proteins that play a significant role in the pathogenesis of NEC is Toll-like receptor 4 (TLR4) which recognizes lipopolysaccharide found in Gram-negative bacteria. In intestinal epithelial cells, a protein encoded by the SIGIRR gene is a major inhibitor of TLR4 signaling. A few SIGIRR variants, including rare p.Y168X and p.S80Y, have already been identified in preterm infants with NEC, but their pathogenic significance remains unclear. This study aimed to investigate the spectrum of SIGIRR genetic variants in term newborns with CHD and to assess their potential association with NEC. Methods and Results: A total of 93 term newborns with critical CHD were enrolled in this study, 33 of them developed NEC. SIGIRR genetic variants were determined by Sanger sequencing of all exons. In total, eight SIGIRR genetic variants were identified, two of which were found only in newborns with NEC (P = 0.12). The rare missense p.S80Y (rs117739035) variant in exon 4 was found in two infants with NEC stage IIA. Two infants with NEC stage III and stage IB carried a novel duplication c. 102_121dup (rs552367848) variant in exon 10 that has not been previously associated with any clinical phenotype. Conclusions : The presence of both variants only in neonates who developed NEC, together with earlier published data, may suggest their potential contribution to the risk of developing NEC in term infants with CHD and allow planning larger cohort studies to clarify their relevance.

The relevance of the research. The risk factors of developing severe thyrotoxic cardiomyopathy (TCMP) are not certainly determined now. But it is essential to choose the optimal approach to care. Recent studies show that even patients of the same sex, with similar age, duration of thyrotoxicosis and hormones’ level differ in a severity of cardiomyopathy. So, scientists began to search for genetic risk predictors of the heart damage, caused by thyrotoxicosis. Among possible genetic predictors of thyrotoxicosis are single nucleotide polymorphisms in genes, that expression is regulated by thyroid hormones or genes, that are involved in developing of non-thyrotoxic cardiac pathology. Aim. To investigate the possible association of the polymorphism Ser38Gly in KCNE1 gene with different manifestations of thyrotoxic cardiomyopathy, especially with atrial fibrillation and cardiac remodeling. Materials and methods. 155 patients with thyrotoxicosis caused by Graves’ disease were enrolled. Genotyping was also made in 187 healthy blood donors – the control group. Genotyping was performed by real time polymerase chain reaction. Results. Our results show an interaction of the single nucleotide polymorphism Ser38Gly in KCNE1 gene with TCMP only in patients aged 45 and older. In this age group atrial fibrillation was significantly more prevalent in GG genotype carriers: 35.3% (GG) vs 13.9% (AG+AA) (p = 0.037). Also, there was a significant difference in systolic blood pressure (SBP) by KCNE1 codon 38 genotypes. SBP were significantly higher in allele G gomozygotes as compared to allele A carriers: 124.89 ± 15.14 mm Hg vs 131.35 ± 15.32 mm Hg (p = 0.012). Conclusion. The fact, that association of the polymorphism Ser38Gly with atrial fibrillation was shown only in group with patients older than 45 years, proves that its influence is of a lower value in comparison with “traditional” risk factors. There was no significant difference among genotypes in severity of TCMP and types of myocardial re-modeling.