MOLECULAR-GENETIC EVALUATION OF CONNECTIVE TISSUE METABOLISM MARKERS COL1A1 AND MMP9 IN CHILDREN WITH VITAMIN D DEFICIENCY AND DISEASES OF THE MUSCULOSKELETAL SYSTEM

Abstract

The connective tissue system, which includes tissues of various functions and structures (cartilage and bone tissue, connective tissue itself, smooth muscles, adipose tissue), takes an active part in the regulatory activity of trophic and metabolic processes. The basis of connective tissue of the body is made up of collagens and provide its strength and elasticity. There is evidence of a high prevalence of dental anomalies, dental caries, periodontal diseases, temporomandibular joint with connective tissue dysplasia. The purpose of this study. Evaluation of the effect of polymorphic variants of the MMP9 a8202g, COL1A1 1546 SP1,G>T genes on the development of vitamin-D deficiency and osteoporosis, which accompanies most diseases of the musculoskeletal system in children. Materials and methods of research. The effect of polymorphic variants of the Col1a1 1546 SP1,G>T, MMP9 a8202g genes was evaluated in the group of patients with vitamin D deficiency (n=10), osteoporosis (n=10) and the control group (n=10). DNA isolation from buccal epithelial cells was performed using a modified Chelex method. Allelic variants of the MMP9 a8202g gene (rs11697325) were evaluated by allele-specific PCR. The frequency of polymorphism of the COL1A1,1 546 (6252) SP1,G>T gene was evaluated by PCR with realtime detection of results and analysis of melting curves. Research results and their discussion. In the Study Group, 60% of children with osteoporosis had the mutant G allele, which is a risk factor for tooth hard tissue diseases and a predictor of osteoporosis. In children with laboratoryconfirmed serum vitamin D deficiency or deficiency, the normal AA genotype of the MMP9 gene was found in 40% of children. In the study groups for OP and vitamin D deficiency, 60% of children had the G allele, which is a risk factor for periodontal disease. In the control group of children, the frequency of the mutant G allele was 65 %. According to the χ2 criterion, the strength of the association between risk factor and morbidity is relatively strong, both for the AA homozygote and the AG mutant heterozygote, and strong for the GG mutant homozygote. Polymorphism of the A8202G MMP9 gene leads to increased cleavage of intercellular matrix proteins and, as a result, destruction of the tissues of the supporting tooth apparatus occurs. In a study of 1546 SP1,g>t polymorphisms of the COL1A1 gene, it was found that GG homozygotes prevailed among the examined children of the control group and children with vitamin D deficiency. In 20% of children-TT homozygotes with osteoporosis according to the criterion χ2, the average binding strength. Mutations in this gene can affect the structural and functional characteristics of the most common bone matrix protein and contribute to the development of osteoporosis. Conclusions. When studying functionally significant polymorphisms of the MMP9 a8202g, COL1A1 1546 SP1,G>T genes included in the connective tissue metabolism gene network in children, it was found that the presence of the G allele of the MMP9 a8202g gene in 40% of children with vitamin D deficiency, 35% of children with OP, and the T allele of the COL1A1 gene in 20% and 40% of the studied children, respectively, lead to a predisposition of these children to carious damage to hard dental tissues and periodontal diseases.