Abstract
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: 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.
Highlights
The exposure to inorganic arsenic species (InAs) such as trivalent (AsIII) and pentavalent (AsV) through drinking groundwater is a global public health issue leading to chronic toxicological effect in humans [1,2,3]
The results showed that the GSTT1-null variant was associated with InAs, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) indicating an increase of InAs (p = 0.04) and MMA (p = 0.01), and a decrease of DMA (p < 0.01)
This study gives additional support regarding the role of single nucleotide polymorphisms (SNPs) on arsenic metabolism and body burden
Summary
The exposure to inorganic arsenic species (InAs) such as trivalent (AsIII) and pentavalent (AsV) through drinking groundwater is a global public health issue leading to chronic toxicological effect in humans [1,2,3]. Inorganic arsenic species are classified by the International Agency for Research on Cancer as Group I type compounds [4]. The World Health Association has recommended a safe level of 10 μg/L as a guideline in drinking water [5]. Reports in several countries of Latin America have shown concentrations of arsenic in groundwater above this risk level [1,6,7,8] and the distribution of arsenic in soils, sediments, vegetables and irrigation water has been recently reviewed in Colombia [9] and Brazil [10]. The presence of arsenic in soils and waters naturally may occur, anthropogenic activities have been the main contributory factor to the environmental contamination by arsenic, soils naturally enriched by arsenic need more attention
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