Polymorphism of p-450 cytochrome detoxication genes in adolescents depending on the degree of contamination of the organism by heavy metals

Introduction. Changes in the body of children and adolescents aimed at adapting to environmental factors are determined by genetic polymorphism in xenobiotic biotransformation genes, determining the degree of susceptibility of the child’s body to pollutants, which is the basis of modern personalized preventive medicine when managing risks to the health of the child population under the influence of environmental factors. Material and methods. Trace elements, including heavy metals, lead and cadmium, were determined in the hair of 256 practically healthy teenagers by atomic absorption spectrophotometry. Depending on the level of content of the latter, two groups of adolescents were formed to determine six genes of the cytochrome P-450 family. Group 1 consisted of adolescents whose cadmium lead content exceeded the average Russian indices. The second group included adolescents whose heavy metals were above the level of average Russian standards. Results. Studies have shown that in adolescents of the 1st group, compared with the data of adolescents of the 2nd group, an increase in the number of carriers of two mutant alleles at the locus rs 1048943 (gene CYP1A1) is 3.08 times, rs 464621 (gene CYP1A1) is 1. 8 times; locus rs 2069522 (CYP1A2 gene) 3.63 times; locus rs 1799853 (CYP2C9 * 2 gene) 4.5 times; locus rs 1057910 (gene CYP2C9 * 3) 3.8 times and locus rs 2279343 (gene CYP2B6) 4.25 times. Moreover, carriers of two normal alleles in adolescents of the first group at the locus rs 1048943 (gene CYP1A1) were 5.14 times; locus rs 2279343 (CYP2B6 gene) was 6.5 fold less than among adolescents of the 2nd group; and at the locus rs 464621 (gene CYP1A1), rs 2069522 (gene CYP1A2), rs 1799853 (gene CYP2C9 * 2), rs 1057910 (gene CYP2C9 * 3) there were no carriers of normal homozygotes. Conclusion. Group 1 adolescents with heavy metal contamination of the body are carriers significantly in a greater number of pathological mutations in the genes of the cytochrome P-450 detoxification system in comparison with data from group 2 adolescents.

Polymorphism of p-450 cytochrome detoxication genes in adolescents depending on the degree of contamination of the organism by heavy metals

Introduction. Changes in the body of children and adolescents aimed at adapting to environmental factors are determined by genetic polymorphism in xenobiotic biotransformation genes, determining the degree of susceptibility of the child’s body to pollutants, which is the basis of modern personalized preventive medicine when managing risks to the health of the child population under the influence of environmental factors. Material and methods. Trace elements, including heavy metals, lead and cadmium, were determined in the hair of 256 practically healthy teenagers by atomic absorption spectrophotometry. Depending on the level of content of the latter, two groups of adolescents were formed to determine six genes of the cytochrome P-450 family. Group 1 consisted of adolescents whose cadmium lead content exceeded the average Russian indices. The second group included adolescents whose heavy metals were above the level of average Russian standards. Results. Studies have shown that in adolescents of the 1st group, compared with the data of adolescents of the 2nd group, an increase in the number of carriers of two mutant alleles at the locus rs 1048943 (gene CYP1A1) is 3.08 times, rs 464621 (gene CYP1A1) is 1. 8 times; locus rs 2069522 (CYP1A2 gene) 3.63 times; locus rs 1799853 (CYP2C9 * 2 gene) 4.5 times; locus rs 1057910 (gene CYP2C9 * 3) 3.8 times and locus rs 2279343 (gene CYP2B6) 4.25 times. Moreover, carriers of two normal alleles in adolescents of the first group at the locus rs 1048943 (gene CYP1A1) were 5.14 times; locus rs 2279343 (CYP2B6 gene) was 6.5 fold less than among adolescents of the 2nd group; and at the locus rs 464621 (gene CYP1A1), rs 2069522 (gene CYP1A2), rs 1799853 (gene CYP2C9 * 2), rs 1057910 (gene CYP2C9 * 3) there were no carriers of normal homozygotes. Conclusion. Group 1 adolescents with heavy metal contamination of the body are carriers significantly in a greater number of pathological mutations in the genes of the cytochrome P-450 detoxification system in comparison with data from group 2 adolescents.

The role of polymorphisms genes of detoxification of xenobiotics in the development of endometriosis

The review presents the results of investigations of gene polymorphism of enzymes involved in estrogen metabolism: CYP1A1, CYP1A2, CYP19 and SULT1A1 in the buccal epithelium samples from 703 women by RFLP (Restriction Fragment Length Polymorphism). The significant association of the presence of allele C and genotype T / C and C / C gene CYP1A1, allele A and genotype C / A and A / A CYP1A2 gene and the T allele and genotype C / T and C / C gene SYP19 with the risk of adenomyosis.

The roles of genes of ksenobiotics biotransformation in the development of predisposition to the toxic heoatitis in workers workers exposed to hepthyle and ethylebenzene-styrene.

Introduction: The aim of this study was to estimate the predisposition of influencing possible factors causing chemical induced abnormal liver function on the basis of studying genes encoding xenobiotic metabolizing enzymes. Methods: Genotyping of CYP1A1, CYP2D6, CYP2E1, EPHX1, NAT2 was performed using polymerase chain reaction and restriction fragment length polymorphism on peripheral leucocyte DNA from 73 incident cases of toxic hepatitis, 163 «groups of risk» on development of a toxic hepatitis, 94 healthy workers and 335 controls.Results and conclusions: No significant association was found between a reference group and petrochemical workers when CYP1A1, CYP2D6, CYP2E1, EPHX1 genotypes were included in the analyses. Among workers was observed the increasing of frequency of a combination *4/*4 genes NAT2 compared with control group. Among the patients with a professional toxic hepatitis are established genetic markers of predisposition to development the disease: Ile/Val gene CYP1A1, Tyr/His gene EPHX1; combinations *4/*7 genes NAT2; and as slow phenotype microsomal epoxide hydrolase; combinations of genotypes IleVal/C1C1 of genes CYP1A1 and CYP2E1; combinations of slow phenotypes microsomal epoxide hydrolase and N-acetyltransferase-2. Our results suggest that genotype Ile/Ile of gene CYP1A1; genotype Tyr/Tyr of gene EPHX1; and as a normal phenotype microsomal epoxide hydrolase; a combination of genotypes IleIle/C1C1 of genes CYP1A1 and CYP2E1; a combination of genotypes IleIle/C1C1/CC/N of genes CYP1A1, CYP2E1, CYP2D6 and a normal phenotype microsomal epoxide hydrolase are protective variants. This study demonstrates a significant combined effect of phase I and phase II polymorphisms on the predisposition of professional pathology at workers exposed to hepthyle and ethylebenzene-styrene.