Генетичні маркери, що визначають ефективність репарації дволанцюгових розривів ДНК і репарації "невідповідностей" ДНК за дії професійних факторів

Abstract

Introduction. Distribution of the following allelic variants of DNA repair genes: АТМ (rs664677), XRCC7 (rs7003908), and MLH1 (rs1799977) in the population of personnel of harmful and hazardous occupation has been studied. The studied polymorphisms are recognized as cancer-specific markers of various types and localization of malignant neoplasms, as well as markers of radiosensitivity/resistance to radiation exposure. Objectives of the work: to find out the significance of polymorphisms of repair genes of double-strand DNA breaks: XRCC7 (rs7003908), АТМ (rs664677), and mismatch repair: MLH1 (rs1799977) in the formation of an individual predisposition to the development of chronic diseases of the bronchopulmonary system in miners and personnel ofasbestos-cement plants. Materials and methods. Respondents of the study group was the personnel of asbestos-cement plants and miners with chronic bronchopulmonary disease; the control group was made up of personnel without diseases of the respiratory system. The genotypes of the following genes were determined by real-time polymerase chain reaction: АТМ (rs664677), XRCC7 (rs7003908), and MLH1 (rs1799977). Results. It was established that the minor alleles of ATM•T and MLH1•G, minor homozygote ATM•TT and heterozygote MLH1•AG are associated with the risk of developing chronic diseases of the bronchopulmonary system. It has been revealed that the dominant alleles of ATM•A, MLH1•A; dominant homozygotes ATM•AA; MLH1•AA and heterozygote ATM•AT contribute to resistance to the development of the respiratory system conditions. Conclusion. The following alleles: ATM•T (Р<=0,06, χ2=3,44; OR=1,44; 95 % Cl: 0,96–2,17); MLH1•G (Р<=0,002, χ2=5,06; OR=1,61; 95 % Cl: 1,04–2,49) and genotype: ATM•TT (Р<=0,01, χ2=6,61; OR=2,48; 95 % Cl: 1,16–5,31); MLH1•AG (Р<=0,002, χ2=9,00; OR=2,32; 95 % CI: 1,29–4,21) associated with the risk of bronchopulmonary conditions development have been established. Also alleles: ATM•A (Р<=0,06, χ2=3,44; OR=0,69; 95 % CI: 0,46–1,04); MLH1•A (Р<=0,002, χ2=5,06; OR=0,62; 95 % CI: 0,40–0,96) and genotype: MLH1•A/A (Р<=0,003, χ2=8,73; OR=0,43; 95 % CI: 0,24–0,79) that form resistance to the development of pulmonary system conditions in certain occupational groups have been established. Key words: SNP, ATM, XRCC7, MLH1, bronchopulmonary pathology.