Analysis of Xenobiotics Biotransformation and DNA Repair Genes as Factors of Aetiology, Pathogenesis and Criteria of Progression in Children with Congenital Spine Deformities

Abstract

Introduction: Spine congenital curvatures formed as a result of anomalies in the development of vertebral bodies leads to severe and rigid deformities of the spinal column in the adolescent age and are often accompanied by irreversible neurologic disorders. Therefore genetic markers study of the congenital malformations is an important and urgent task. Aim: The aim of the study is to determine the frequency of detoxification and reparation genes polymorphism in congenital spine deformities patients. Materials and Methods: The study of 200 children with Congenital Spine Deformities (CSD) between the age of 1 year 2 months to 16 years and 96 healthy children aged from 2 to 16 years without pathology of the spine was carried out by the methods of clinical and radiographic diagnostics. Molecular diagnostics was carried out by analysing multiple polymorphic regions in the genes of detoxification and DNA repair, which are of clinical importance due to their predisposing factors in various congenital malformations. Genotyping of the gene polymorphism was performed using Polymerase Chain Reaction (PCR) and the PCR products were visualised by gel electrophoresis. Results: The polymorphisms of the genes CYP1A2, GSTM1, GSTT1, GSTP1, NAT2, XRCC1, XRCC3 and their frequency distribution among patients with CSD and control group were investigated. Significant differences in the distribution of genotypes compared with the control group were found in the polymorphic regions of the genes CYP1A2, GSTM1, GSTT1, NAT2, XRCC3. However, in the GSTP1 and XRCC1 genes, no significant differences between the CSD patients and the control group was observed. Conclusion: All patients with congenital spine deformities had significant changes in some candidate genes alleles. It was found that the number of minor alleles in the genes under investigation correlate with the severity of congenital deformity and the variability of vertebral anomalies. It was determined that in children with multiple and combined defects in the spine development, there is a greater number of mutations in the detoxification and DNA-repair genes compared to children with isolated vertebral anomalies.

Keywords

• children
• dna repair
• detoxification
• molecular diagnostics