Molecular genetic analysis of genes for detoxification and DNA repair in children with congenital deformities of the thoracic and lumbar spine

Abstract

Introduction. Spine congenital curvatures, which form from anomalies in the development of vertebral bodies, comprise 3.2% of the general structure of vertebral column deformities. Several such anomalies present during adolescence lead to severe and rigid curvature of the spinal column and are often accompanied by irreversible neurological disorders. The timely detection of the progressive forms of curvature and early surgical treatment are measures that prevent against neurological deficit development and gross congenital deformities of the spine in children. However, it is extremely difficult to predict the course of congenital spinal column deformation in infants based on clinical and radiological investigations alone. Therefore, the study of congenital malformation genetic markers is an essential and immediate task.
 Materials and methods. Two hundred 1.2–16-year-old children with congenital deformities of the thoracic and lumbar spine were examined using clinical and radiation diagnostic methods. Molecular genetic studies were performed by analyzing several polymorphic regions in the genes for the first and second stages of detoxification and DNA repair, which are of clinical importance as predisposing factors in several congenital malformations. Polymorphisms were determined using the polymerase chain reaction (PCR) method. The results were determined using gel electrophoresis of DNA in a polyacrylamide gel.
 Results and discussion. The polymorphisms of the genes CYP1A2, NAT2, GSTM1, GSTT1, GSTP1, XRCC1, XRCC3 and their frequency distributions among patients with congenital spine deformities (CSD) were studied. The results for each gene are presented in the digital diagrams, and their indicators are compared with the values of the control group.
 Conclusion. In most patients (83%) with spinal congenital deformations, there were mutations of candidate genes in the homozygous state; however, the simultaneous carriage of several mutant alleles in patients with CSD was more than twice that in the control group. Children with multiple and combined defects in spine development noted the presence of more mutations in the genes for detoxification and DNA repair. The obtained results already assume to a certain extent the course of the spine congenital deformity in patients at an early age. However, the final evaluation and identification of molecular genetic criteria for the progressive course of spine congenital deformities in children requires further study.