Molecular Genetic Research of GSTM, GSTT and VDR genes

According to the “threshold” model of multifactorial diseases, genetic and epigenetic factors determine each person's predisposition to developing a disease. If this total predisposition exceeds a certain threshold, the disease develops. The aim of study to investigate the frequency of polymorphic loci TaqI and Apa I of the VDR-3 gene and deletion loci of the genes GSTM1 0 and GSTT1 0 (glutathione-S-transferases) in the genotype of children with dysmetabolic nephropathy. Materials and methods. A molecular genetic study of the Taq I polymorphic locus was conducted in 55 children with different severity of dysmetabolic nephropathy: 35 children with complicated dysmetabolic nephropathy and 20 children with uncomplicated DN; the results were compared with the data of 44 healthy children. Results. We have established an association of dysmetabolic nephropathy with the presence of deletion alleles of GSTM1 0/0 and GSTT1 0/0 in the child's genotype, a significant association of the frequency of simultaneous carriage of deletion alleles GSTT1 0/0+GSTM1 0/0 with a more severe course of DN in children. The ability of the products of these genes to provide cellular resistance to lipid peroxidation free radicals and prevent damage to the HDC was investigated, and it was concluded that the null alleles of GSTM1 0/0 GSTT1 0/0 and, especially, their combination GSTT1 0/0+GSTM1 0/0 may be modifier genes in the pathogenesis of dysmetabolic nephropathy in children. Conclusions. Molecular genetic analysis of polymorphic variants of the VDR3 gene showed a difference in the frequency of VDR3 alleles and genotypes between children with dysmetabolic nephropathy and healthy children. This confirms that allelic variance in the VDR3 gene may be a risk factor for developing dysmetabolic nephropathy, and the gene itself may be considered a candidate gene in the pathogenesis of multifactorial inheritance of dysmetabolic nephropathy. The results obtained may further form the basis of screening tests for diagnosing dysmetabolic nephropathy in children.