As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater
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González Martínez, Farith
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As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater
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The urinary arsenic metabolites may vary among individuals and the genetic factors have been reported to explain part of the variation. We assessed the influence of polymorphic variants of Arsenic-3-methyl-transferase and Glutathione-S-transferase on urinary arsenic metabolites. Twenty-two groundwater wells for human consumption from municipalities of Colombia were analyzed for assessed the exposure by lifetime average daily dose (LADD) (mu g/kg bw/day). Surveys on 151 participants aged between 18 and 81 years old were applied to collect demographic information and other factors. In addition, genetic polymorphisms (GSTO2-rs156697,GSTP1-rs1695,As3MT-rs3740400,GSTT1andGSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: As-III, As-V, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured using HPLC-HG-AFS. The influence of polymorphic variants, LADD and other factors were tested using multivariate analyses. The median of total arsenic concentration in groundwater was of 33.3 mu g/L and the median of LADD for the high exposure dose was 0.33 mu g/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes ofAs3MTcompared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes ofGSTP1compared to the wild-type genotype. Both DMA and MMA concentrations were higher inGSTM1-nullgenotypes compared to the active genotype. Multivariate analyses showed statistically significant association among interactions gene-gene and gene-covariates to modify the MMA and DMA excretion. Interactions between polymorphic variantsAs3MT*GSTM1andGSTO2*GSTP1could be potential modifiers of urinary excretion of arsenic and covariates as age, LADD, and alcohol consumption contribute to largely vary the arsenic individual metabolic capacity in exposed people.
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Ministerio de Ciencia, Tecnologia e Innovacion (MinCiencias) in Colombia
110777757778
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Artículo de publicación ISI Artículo de publicación SCOPUS
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Int. J. Mol. Sci. 2020, 21, 4832
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