Polymorphic CYPs and GSTs genes’ loci in workers exposed to chronic mercury vapor exposure
- Authors: Chernyak Y.I.1
-
Affiliations:
- East-Siberian Institute of Medical and Ecological Research
- Issue: Vol 97, No 10 (2018)
- Pages: 921-924
- Section: INTOXICATION AND EMPLOYEES' HEALTH
- Published: 22.10.2020
- URL: https://ruspoj.com/0016-9900/article/view/640485
- DOI: https://doi.org/10.47470/0016-9900-2018-97-10-921-924
- ID: 640485
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Full Text
Abstract
Introduction. The study investigated the association between polymorphic loci of xenobiotics biotransformation genes and the development of the chronic mercury intoxication (CMI) in a cohort of 120 former male workers of caustic soda production plant, who had been chronically exposed to mercury vapor.
Material and methods. The polymorphic variants of CYP1A1 (+462Ile/Val, rs1048943), CYP1A2*F (-163C/A, rs762551), CYP2E1 (+1053C/T, rs2031920), GSTM1 and GSTT1 genes were studied. The workers were divided into two groups: group 1 included 46 subjects who had contact with mercury but without the diagnosis of CMI; group 2 consisted of 74 patients in the remote period of CMI. Two-tailed Fisher’s exact test was used to estimate group differences in allele and genotype frequencies, as well as the logistic regression analysis for 4 genetic models to detect associations of studied polymorphic loci along with the development of CMI.
Results. The prevalence of IleVal heterozygote in group of workers without the disease (group 1, n = 46) was found to be higher (p = 0.01) if compared to patients with CMI diagnosis (group 2, n = 74), and there was revealed also the inverse association between IleVal-CYP1A1 (+ 462Ile/Val) genotype and the development of CMI (OR = 0.10, 95% CI 0.02-0.48, p <0.001). The lack of carriers of ValVal homozygotes in the examined cohort was determined. Such data show the IleVal genotype to be a marker of resistance to disease development.
Conclusion. The obtained results indicate that the polymorphic locus CYP1A1 (+ 462 Ile/Val) could be significant in the mechanisms of CMI development which promotes the search for effective criteria for assessing individual’s susceptibility and the risk of the development of this pathology.
About the authors
Yury I. Chernyak
East-Siberian Institute of Medical and Ecological Research
Author for correspondence.
Email: yuri_chernyak@hotmail.com
ORCID iD: 0000-0001-9641-0327
MD, Ph.D., DSc, Leading researcher of the Laboratory of Immunological, biochemical, molecular and genetic research of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation.
e-mail: yuri_chernyak@hotmail.com
Russian FederationReferences
- Lakhman O.L., Katamanova E.V., Konstantinova T.N., Shevchenko O.I., Meshcheryagin V.A., Andreeva O.K. et al. Contemporary approaches to the classification of occupational mercury intoxication. Ecologiya cheloveka 2009; 12: 22–27. (in Russian)
- Tiunov L.A. Mechanisms of natural detoxication and antioxidant protection. Vestnik Rossiiskoi akademii meditsinskikh nauk 1995; 3: 9-13. (in Russian)
- Lewis D.F.V. Guide to cytochromes P450 structure and function. London and New York: Taylor & Francis: 2001.
- Stavrinou P., Mavrogiorgou M.C., Polyzoidis K., Kreft-Kerekes V., Timmer M., Marselos M. et al. Expression profile of genes related to drug metabolism in human brain tumors. PLoS One. 2015; 10(11): e0143285. https://doi.org/10.1371/journal.pone.0143285
- Dutheil F., Beaune P., Loriot M.A. Xenobiotic metabolizing enzymes in the central nervous system: Contribution of cytochrome P450 enzymes in normal and pathological human brain. Biochimie. 2008; 90 (3): 426-36. https://doi.org/10.1016/j.biochi.2007.10.007
- Ferguson C.S., Tyndale R.F. Cytochrome P450 enzymes in the brain: emerging evidence of biological significance. Trends Pharmacol Sci. 2011; 32(12): 708-14. https://doi.org/10.1016/j.tips.2011.08.005
- Ghosh C., Hossain M., Solanki J., Dadas A., Marchi N., Janigro D. Pathophysiological implications of neurovascular P450 in brain disorders. Drug Discov Today. 2016; 21 (10): 1609-19. https://doi.org/10.1016/j.drudis.2016.06.004
- Ravindranath V., Strobel H.W. Cytochrome P450-mediated metabolism in brain: functional roles and their implications. Expert Opin Drug Metab Toxicol. 2013; 9 (5): 551-8. https://doi.org/10.1517/17425255.2013.759208
- Chernyak Yu.I., Itskovich V.B., D’yakovich O.A., Kolesnikov S.I. Role of cytochrome P450-dependent monooxygenases and polymorphic variants of GSTT1 and GSTM1 genes in the formation of brain lesions in individuals chronically exposed to mercury. Bull Exp Biol Med. 2013; 156 (1): 15-18. https://doi.org/10.1007/s10517-013-2266-2
- Nakahama T., Inouye Y., Fukuhara M. Comparative study on in vitro inhibitory effects of heavy metals on rabbit drug-metabolizing enzymes. J Health Science. 2001; 47(1): 14-20.
- Llop S., Ballester F., Broberg K. Effect of gene-mercury interactions on mercury toxicokinetics and neurotoxicity. Curr Environ Health Rep. 2015; 2(2): 179-94. https://doi.org/10.1007/s40572-015-0047-y
- Custodio H.M., Harari R., Gerhardsson L., Skerfving S., Broberg K. Genetic influences on the retention of inorganic mercury. Arch Environ Occup Health. 2005; 60 (1): 17-23. https://doi.org/10.3200/AEOH.60.1.17-23
- Gundacker C., Komarnicki G., Jagiello P., Gencikova A., Dahmen N., Wittmann K.J. et al. Glutathione-S-transferase polymorphism, metallothionein expression, and mercury levels among students in Austria. Sci Total Environ. 2007; 385 (1-3): 37-47. https://doi.org/10.1016/j.scitotenv.2007.07.033
- Chernyak Yu.I., Merinova A.P. HSP70 (HSPA1) polymorphisms in former workers with chronic mercury vapor exposure. Int J Occup Med Environ Health. 2017; 30 (1): 77-85. https://doi.org/10.13075/ijomeh.1896.00732
- Grigorieva S.A., Nikitina V.A., Kosyakova N.V., Kirillov A.V., Aksenova M.G., Sidorova I.E et al. Polymorphism frequencies of xenobiotic biotransformation enzymes genes CYP1A1, GSTT1 and GSTM1 in a population of Moscow. Meditsinskaya genetika. 2007; 6 (3): 38-42. (in Russian)
- Pirmohamed M., Kitteringham N.R., Quest L.J., Allott R.L., Green V.J., Gilmore I.T. et al. Genetic polymorphism of cytochrome P4502E1 and risk of alcoholic liver disease in Caucasians. Pharmacogenetics. 1995; 5 (6): 351-7.
- Chida M., Yokoi T, Fukui T, Kinoshita M., Yokota J., Kamataki T. Detection of three genetic polymorphisms in the 5′-flanking region and intron 1 of human CYP1A2 in the Japanese population. Jpn J Cancer Res. 1999; 90: 899-902. https://doi.org/10.1111/j.1349-7006.1999.tb00832.x
- Ambrosone C.B., Sweeney C., Coles B.F., Thompson P.A., McClure G.Y., Korourian S. et al. Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer. Cancer Res. 2001; 61 (19): 7130-5.
- Solé X., Guinó E., Valls J., Iniesta R., Moreno V. SNPStats: A web tool for the analysis of association studies. Bioinformatics. 2006; 22: 1928-9. https://doi.org/10.1093/bioinformatics/btl268
- Toselli F., Dodd P.R., Gillam E.M. Emerging roles for brain drug-metabolizing cytochrome P450 enzymes in neuropsychiatric conditions and responses to drugs. Drug Metab Rev. 2016; 48(3): 379-404. https://doi.org/10.1080/03602532.2016.1221960
- Concise international chemical assessment document 50. Elemental mercury and inorganic mercury compounds: human health aspects. WHO, Geneva, Switzerland, 2003. URL: http://www.who.int/ipcs/publications/cicad/en/cicad50.pdf (accessed: 26.03.2018).
- Rand M.D., Lowe J.A., Mahapatra C.T. Drosophila CYP6g1 and its human homolog CYP3A4 confer tolerance to methylmercury during development. Toxicology. 2012; 300(1-2): 75-82. https://doi.org/10.1016/j.tox.2012.06.001
- Llop S., Tran V., Ballester F., Barbone F., Sofianou-Katsoulis A., Sunyer J. et al. CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment. Environ Int. 2017; 105: 34-42. https://doi.org/10.1016/j.envint.2017.04.013
- Gundacker C., Gencik M., Hengstschläger M. The relevance of the individual genetic background for the toxicokinetics of two significant neurodevelopmental toxicants: mercury and lead. Mutat Res. 2010; 705(2): 130-40. https://doi.org/10.1016/j.mrrev.2010.06.003
- Andreoli V., Sprovieri F. Genetic aspects of susceptibility to mercury toxicity: An overview. Int J Environ Res Public Health. 2017; 14(1): 25 p. https://doi.org/10.3390/ijerph14010093
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