Role of intergenic interactions between cytokine and Toll-like receptor genes in the etiology of congenital heart defects

The incidence of congenital heart defects (CHDs) reaches 1% of all newborns. Of particular importance is the group of heart defects without a family history and chromosomal disorders, which makes up>80% of all CHDs. These heart defects can be designated as sporadic CHDs, and their etiology and pathogenesis continue to be studied. Aim. To study the association of cytokine and Toll-like receptor (TLR) genes with CHDs in children. Material and methods. We examined 188 children with sporadic (without family history) CHDs (main group) and 103 healthy children without CHDs (control group). Genotyping was performed by real-time polymerase chain reaction (PCR). Results. Sporadic CHDs, in general, and septal CHDs, in particular, are formed on similar intergenic associations that determine the dysregulation of the proliferation and differentiation of progenitor cells of the cardiovascular system. Probably, one of the molecular mechanisms for sporadic septal CHDs may be the inefficiency of intracellular signaling pathways for Nuclear Factor kappa B (NF-κB) due to the primary deficiency of membrane heterodimers TLR1/TLR6, TLR2/TLR6, and TLR1/TLR2. Conclusion. Data on altered proinflammatory potential in the group of sporadic septal CHDs should be taken into account in the postnatal period when conducting cardiac surgery.