As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater

International Journal of Molecular Sciences

Daniel Sánchez-Rodas¹  Farith González-Martínez²  Boris Johnson-Restrepo²  ChristopherA. Sandoval³  LuisA. Quiñones⁴  NelsonM. Varela⁴ 

[1] Center for Research in Sustainable Chemistry, CIQSO, University of Huelva, 21071 Huelva, Spain;Environmental Chemistry Research Group and Public Health Research Group, University of Cartagena, Cartagena 130015, Colombia;Laboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic-Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago 8320000, Chile;Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), 28015 Madrid, Spain;

关键词: arsenic;    urinary arsenic metabolites;    arsenic speciation;    polymorphic variants;    arsenic-3-methyl-transferase;    glutathione-S-transferase;   

DOI  :  10.3390/ijms21144832

来源: DOAJ

【 摘 要 】

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) (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: 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 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.

【 授权许可】

Unknown