Features of polymorphic site combinations of Toll-like receptor (TLR) genes in children with ventricular septal defects

Congenital heart disease is the leading cause of the childhood disability and mortality. The development of new technologies has made it possible to advance in diagnosis and treatment of congenital heart disease, but its etiology is poorly understood. Considering multifactorial origin of this disease, a search for biomarkers having fundamental and practical importance is of current interest. Study of the genetic component is one of the areas of research. E.g., Toll-like receptors (TLR) are important regulators of susceptibility to infectious and non-infectious diseases. Polymorphic variants with single nucleotide substitutions in these genes may be accompanied by changes in the structure and expression of the encoded proteins, thus affecting functional activity of these receptors. Our aim was to study some genetic predictors of congenital heart defects in children. Materials and methods. We examined 47 children (21 girls and 26 boys) with congenital heart defects: 23 children had a ventricular septal defect (VSD); 24 children, atrial septal defect (ASD). The patients in the main group were 1 to 9 years old. As a control group, 96 conditionally healthy age- and sex-matched children were examined. Real-time genotyping was carried out with Viia7 real-time PCR system (Applied Biosystems, USA) using TaqMan probes of four TLR genes (TLR1 rs5743611, rs5743551, TLR2 rs5743708, rs3804099, TLR4 rs4986791, rs4986790, TLR6 rs3775073, rs5743810). Results. The distribution of all studied polymorphic variants corresponded to the HardyWeinberg equilibrium. It was revealed that sporadic nonsydromal VSD are associated with G allele of the TLR2 gene (rs5743708) and T allele of the TLR6 gene (rs3775073). According to ROC analysis, the combination of these alleles is a significant parameter showing high degree of sensitivity (82.4%). Both TLR2 (rs5743708) and TLR6 (rs3775073) gene variants define amino acid substitutions (missense mutations) in TLR molecules. Thus, we concluded that genetic testing can be used to identify risk groups at the early stages.