GENOMIC, TRANSCRIPTOMIC AND PROTEOMIC TECHNOLOGIES AS A MODERN TOOL FOR HEALTH DISORDERS DIAGNOSTICS, ASSOCIATED WITH THE IMPACT OF ENVIRONMENTAL FACTORS

Abstract

Introduction. Today, it is relevant to use modern critical technologies for identifying and evaluating the negative effects associated with the effects of chemicals at the stages of pre-nosological changes. This improves the efficiency of the early detection of progress in pre-pathological conditions prior to the onset of pronounced functional changes and the aggravation of the disease. The use of molecular diagnostic methods based on genomic, transcriptomic, and proteomic analysis technologies is one of the most promising approaches. Aim of the work is an analysis of both aspects and practical use of the modern critical technologies capabilities (genomic, transcriptomic and proteomic technologies) in the implementation of biomedical and experimental studies for the tasks of the detection biomarkers of negative effects of chemical risk factors on the example of exposure conditions with aluminum compounds. Material and methods. The proteomic analysis was carried out by the method of two-dimensional electrophoresis, polymorphism of alleles and genotypes of candidate genes by a real-time polymerase chain reaction. The transcriptome state was assessed based on the results of gene expression studies. The expression of membrane and serum proteins was studied by biochemical and immunological methods analysis. Statistical processing of the results was carried out in the systems “Gencalculator,” “Gene Expert” and online program “SNPStats”. Results. The results of using proteomic analysis technologies made it possible to identify proteins annexin-13, SH3-domain protein-RF3, cathepsin L1 and, accordingly, genes CTSL, SH3RF3, THO complex subunit 2 as Ohmic markers of aerogenic exposure of inorganic compounds. The results of the analysis of gene polymorphism in the population exposed to environmental pollution allowed establishing the changed frequency of variant alleles and genotypes of genes: immune control - TLR4 (toll-like receptor); vascular factors - eNOS rs1799983 (endothelial NOsintase); detoxification - coproporphyrinogen oxidase CPOX (rs1131857), cytochrome P450 CYP1A1 (rs 1048943); neuro-humoral regulation of ANKK1 rs1800497 (dopamine receptor gene) and HTR2A rs7997012 (serotonin receptor gene). The results of gene expression analysis made it possible to establish negative transcriptomic effects induced by exposure to amphoteric metals due to the isolation of specific CD4+, CD8+, CD16+ cell phenotypes expressing the proteomic profile gene of blood plasma lipoprotein A (LPA gene). Discussion. The obtained results correspond data of a number of scientific studies, noting the importance of identifying polymorphic deviations of genes determining the individual risk of health problems in a variety of stressful environmental factors affecting humans. Minor genotypes of candidate genes under conditions of excessive contamination with amphoteric metal compounds significantly increase the risk of deviations in immune regulation indices, which modifies apoptosis mechanisms, which are crucial for the formation of atopy and onco-proliferation. Conclusion. The use of genome, transcriptomic and proteomic technologies as a modern tool for the diagnostics of health disorders allowed justifying the set of priority exposition and effect Ohmic-markers, associated with aerogenic effect of amphoteric metals, which have a modifying effect on the pathogenetic mechanisms of the formation of disorders of nervous and immune systems, the 1st and 2nd phase of detoxification, the likelihood of vascular disorders and onco-proliferative processes.