Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)

Chloroform accumulation in the body and the increase in its steady-state concentrations in blood of exposed people have been established to be associated with polymorphisms of enzyme genes in a genotype involved in metabolism of water disinfection byproducts (A415G of EPHX1 gene, C1091T of CYP2E1 ge...

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Main Authors: E.V. Drazdova, K.V. Kaliasniova, V.E. Syakhovich, N.А. Dalhina
Format: Article
Language:English
Published: FBSI “Federal Scientific Center for Medical and Preventive Health Risk Management Technologies” 2023-03-01
Series:Analiz Riska Zdorovʹû
Subjects:
Online Access:https://journal.fcrisk.ru/eng/2023/1/15
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author E.V. Drazdova
K.V. Kaliasniova
V.E. Syakhovich
N.А. Dalhina
author_facet E.V. Drazdova
K.V. Kaliasniova
V.E. Syakhovich
N.А. Dalhina
author_sort E.V. Drazdova
collection DOAJ
description Chloroform accumulation in the body and the increase in its steady-state concentrations in blood of exposed people have been established to be associated with polymorphisms of enzyme genes in a genotype involved in metabolism of water disinfection byproducts (A415G of EPHX1 gene, C1091T of CYP2E1 gene, zero mutations of GSTT1 and GSTM1 genes) (р < 0.000001). These polymorphisms in a genotype correlate with higher chloroform levels in blood of people consuming chlorinated drinking water: by 43.8 % and higher for GSTM1 gene polymorphism; by 68.2 % and higher for GSTT1; by 80.4 % and higher for EPHX1 (р < 0.01). EPHX1 genetic polymorphism makes chloroform accumulation much more probable (levels in blood ≥ Р75), which is the most pronounced when combined with GSTТ1 genetic polymorphism. The study results allow us to consider hetero- and homozygous polymorphic genotypes AG/GG for the EPHX1 gene, CT/TT for the CYP2E1 gene, and the null allele in the GSTT1 and GSTM1 genes as genetic predisposition factors for chloroform accumulation in the body. This increases the probability of health outcomes associated with chronic exposure to this disinfection byproduct. The A415G polymorphism of the EPHX1 gene and null alleles of GSTT1 gene, their combinations including the combination with the null allele of the GSTM1 gene and/or the C1091T polymorphism of the CYP2E1 gene can be used as the most informative biomarkers of sensitivity when assessing risks associated with exposure to trihalomethanes (chloroform) at levels not exceeding MPC in water.
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spelling doaj.art-bbfa553c25fc4f31b928a6aa516bb0952023-06-08T08:25:48ZengFBSI “Federal Scientific Center for Medical and Preventive Health Risk Management Technologies”Analiz Riska Zdorovʹû2308-11552308-11632023-03-01114615910.21668/health.risk/2023.1.15.engPolymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)E.V. Drazdova0K.V. Kaliasniova1V.E. Syakhovich2N.А. Dalhina3Scientific and Practical Center for Hygiene, 8 Akademicheskaya Str., Minsk, 220012, Republic of BelarusScientific and Practical Center for Hygiene, 8 Akademicheskaya Str., Minsk, 220012, Republic of BelarusNational Anti-Doping Laboratory, 31 ag. Lesnoi, Minsk region, 223040, Republic of BelarusScientific and Practical Center for Hygiene, 8 Akademicheskaya Str., Minsk, 220012, Republic of BelarusChloroform accumulation in the body and the increase in its steady-state concentrations in blood of exposed people have been established to be associated with polymorphisms of enzyme genes in a genotype involved in metabolism of water disinfection byproducts (A415G of EPHX1 gene, C1091T of CYP2E1 gene, zero mutations of GSTT1 and GSTM1 genes) (р < 0.000001). These polymorphisms in a genotype correlate with higher chloroform levels in blood of people consuming chlorinated drinking water: by 43.8 % and higher for GSTM1 gene polymorphism; by 68.2 % and higher for GSTT1; by 80.4 % and higher for EPHX1 (р < 0.01). EPHX1 genetic polymorphism makes chloroform accumulation much more probable (levels in blood ≥ Р75), which is the most pronounced when combined with GSTТ1 genetic polymorphism. The study results allow us to consider hetero- and homozygous polymorphic genotypes AG/GG for the EPHX1 gene, CT/TT for the CYP2E1 gene, and the null allele in the GSTT1 and GSTM1 genes as genetic predisposition factors for chloroform accumulation in the body. This increases the probability of health outcomes associated with chronic exposure to this disinfection byproduct. The A415G polymorphism of the EPHX1 gene and null alleles of GSTT1 gene, their combinations including the combination with the null allele of the GSTM1 gene and/or the C1091T polymorphism of the CYP2E1 gene can be used as the most informative biomarkers of sensitivity when assessing risks associated with exposure to trihalomethanes (chloroform) at levels not exceeding MPC in water. https://journal.fcrisk.ru/eng/2023/1/15cyp2e1gstm1gstt1ephx1 genesdisinfection byproductsdrinking watergene polymorphismbiomonitoringhealth risk assessmentbiomarkers of susceptibility
spellingShingle E.V. Drazdova
K.V. Kaliasniova
V.E. Syakhovich
N.А. Dalhina
Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)
Analiz Riska Zdorovʹû
cyp2e1
gstm1
gstt1
ephx1 genes
disinfection byproducts
drinking water
gene polymorphism
biomonitoring
health risk assessment
biomarkers of susceptibility
title Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)
title_full Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)
title_fullStr Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)
title_full_unstemmed Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)
title_short Polymorphisms of xenobiotic metabolism enzyme genes cyp2e1, gstm1, gstt1, ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts (using chloroform as an example)
title_sort polymorphisms of xenobiotic metabolism enzyme genes cyp2e1 gstm1 gstt1 ephx1 as biomarkers of sensitivity to exposure to water disinfection byproducts using chloroform as an example
topic cyp2e1
gstm1
gstt1
ephx1 genes
disinfection byproducts
drinking water
gene polymorphism
biomonitoring
health risk assessment
biomarkers of susceptibility
url https://journal.fcrisk.ru/eng/2023/1/15
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