González Martínez, FarithSánchez-Rodas Navarro, Daniel AlejandroVarela, NelsonSandoval, ChristopherQuiñones, LuisJohnson-Restrepo, Boris2020-10-082020-10-082020-07González Martínez, F., Sánchez Rodas, D., Varela, N. M., Sandoval, C. A., Quiñones, L. A., & Johnson-Restrepo, B. (2020). As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater. International Journal of Molecular Sciences, 21(14), 4832. DOI: https://doi.org/10.3390/ijms211448321422-0067http://hdl.handle.net/10272/18845The 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) (μg/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, GSTT1 and GSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: AsIII, AsV, 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 μg/L and the median of LADD for the high exposure dose was 0.33 μg/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes of As3MT compared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes of GSTP1 compared to the wild-type genotype. Both DMA and MMA concentrations were higher in GSTM1-null genotypes 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 variants As3MT*GSTM1 and GSTO2*GSTP1 could 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.engAtribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ArsenicUrinary arsenic metabolitesArsenic speciationPolymorphic variantsArsenic-3- methyl-transferaseGlutathione-S-transferasejournal article10.3390/ijms21144832open access