medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2018-97-10-921-924medlit-994Research ArticleИНТОКСИКАЦИЯ И ЗДОРОВЬЕ РАБОТНИКОВINTOXICATION AND EMPLOYEES' HEALTHПолиморфные локусы CYPs и GSTs генов у лиц, подвергшихся хроническому воздействию паров металлической ртутиPolymorphic CYPs and GSTs genes’ loci in workers exposed to chronic mercury vapor exposurehttps://orcid.org/0000-0001-9641-0327ЧернякЮрий ИльичChernyakYury I.

Доктор биол. наук, вед. науч. сотр. лаб. иммуно-биохимических и молекулярно-генетических исследований ФГБНУ «Восточно-Сибирский институт медико-экологических исследований».

e-mail: yuri_chernyak@hotmail.com

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

yuri_chernyak@hotmail.comФГБНУ «Восточно-Сибирский институт медико-экологических исследований»РоссияEast-Siberian Institute of Medical and Ecological ResearchRussian Federation2018221020209710921924Copyright © Черняк Ю.И., 20202020Черняк Ю.И.Chernyak Y.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/994Введение

Введение. В работе исследовали ассоциацию полиморфных локусов генов системы биотрансформации ксенобиотиков с формированием хронической ртутной интоксикации (ХРИ) в когорте бывших работников производства каустика, подвергшихся хроническому воздействию паров ртути. 

Материал и методы

Материал и методы. Полиморфные варианты CYP1A1 (+462Ile/Val, rs1048943), CYP1A2*F (-163C/A, rs762551), CYP2E1 (+1053C/T, rs2031920), GSTM1 и GSTT1 генов изучены у 120 мужчин, распределённых в две группы: группа 1 (n = 46) – стажированные работники, контактировавшие с ртутью и не имеющие диагноза ХРИ, группа 2 (n = 74) – больные в отдалённом периоде ХРИ. Использовали точный критерий Фишера (двусторонний тест) для оценки различий между группами по частотам аллелей и генотипов, а также логистическую регрессию для обнаружения ассоциаций изученных полиморфных локусов с ХРИ для четырёх видов генетических моделей. 

Результаты

Результаты. Выявлена повышенная частота (p = 0,01) носительства IleVal гетерозиготы в группе стажированных работников относительно пациентов с диагнозом ХРИ, а также обратная ассоциация IleVal-CYP1A1 (+462Ile/Val) генотипа с развитием ХРИ (OR = 0,10, 95 % CI 0,02-0,48, p < 0,001) на фоне отсутствия в когорте носителей ValVal гомозиготы. Такие данные указывают на то, что IleVal генотип является маркером устойчивости к формированию заболевания. 

Обсуждение

Обсуждение. Результаты обсуждаются в контексте гипотезы о способности CYP3A генов модифицировать ответ на воздействие метилртути на раннем этапе развития нервной системы. 

Заключение

Заключение. Полученные результаты свидетельствуют о возможной заинтересованности полиморфного локуса CYP1A1 (+462Ile/Val) в механизмах формирования и прогрессирования ХРИ, что будет способствовать выработке критериев оценки индивидуальной чувствительности организма и риска развития этого заболевания.

Introduction

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

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

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

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.

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The authors declare that there are no conflicts of interest present.