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. 2020 Jul 8;21(14):4832.
doi: 10.3390/ijms21144832.

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

Farith González-Martínez  1   2 , Daniel Sánchez-Rodas  3 , Nelson M Varela  2   4 , Christopher A Sandoval  4 , Luis A Quiñones  2   4 , Boris Johnson-Restrepo  1
Affiliations

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

Farith González-Martínez et al. Int J Mol Sci. .

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.

Keywords: arsenic; arsenic speciation; arsenic-3-methyl-transferase; glutathione-S-transferase; polymorphic variants; urinary arsenic metabolites.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The classical pathway for explain the mechanism of arsenic metabolism. The AsV is reducing to AsIII through a conjugation reaction among Glutathione (GSH as the electron donor) and Glutathione-S-transferase enzymes (GSTP1), as well as purine nucleoside phosphorylase (PNP) enzymes. AsIII species are methylated to monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV). The enzyme participant is Arsenic (+3)-methyl-transferase (As3MT), using S-adenosyl-methionine (SAM-methyl donor). GSH and GSTO1–2 involve in a conjugated reaction to form the intermediate products monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII). The MMAV reductase enzyme is responsible for the reduction of MMAV to MMAIII.
Figure 2
Figure 2
Multivariate Dirichlet regression on the relationship among the urinary arsenic metabolites and total urinary As concentration by genotype adjusted. (A) Wild-type genotype of GSTO2: InAs (p < 0.01), MMA (p = 0.01) and DMA (p < 0.01). (B) Heterozygous+ homozygous genotypes of GSTO2: InAs (p = 0.27), MMA (p < 0.01) and DMA (p = 0.01). C. Wild-type genotype of GSTP1: InAs (p = 0.51), MMA (p = 0.02) and DMA (p = 0.03). D. Heterozygous + homozygous genotypes of GSTP1: InAs (p = 0.15), MMA (p < 0.01) and DMA (p < 0.01).
Figure 3
Figure 3
Multivariate Dirichlet regression on the relationship among the urinary arsenic metabolites and urinary As concentration by genotype adjusted. (A) Active GSTT1: InAs (p = 0.70), MMA (p = 0.03), DMA (p = 0.05). (B) Null GSTT1: InAs (p = 0.71), MMA (p = 0.07), DMA (p = 0.08) (C) Active GSTM1: InAs (p = 0.32), MMA (p = 0.38), DMA (p = 0.53) (D) Null GSTM1: InAs (p = 0.06), MMA (p < 0.01), DMA (p < 0.01).
Figure 4
Figure 4
Multivariate Dirichlet regression on the relationship among the urinary arsenic metabolites and urinary As concentration by genotype adjusted. (A) Wild-type genotype of As3MT; InAs (p = 0.18), MMA (p < 0.01), DMA (p < 0.01). (B) Heterozygous+ homozygous genotypes of As3MT: InAs (p = 0.70), MMA (p = 0.06), DMA (p = 0.08).
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References

    1. Caceres D.D., Pino P., Montesinos N., Atalah E., Amigo H., Loomis D. Exposure to inorganic arsenic in drinking water and total urinary arsenic concentration in a Chilean population. Environ. Res. 2005;98:151–159. doi: 10.1016/j.envres.2005.02.007. - DOI - PubMed
    1. Caceres D.D., Werlinger F., Orellana M., Jara M., Rocha R., Alvarado S., Quiñones L. Polymorphism of Glutathione S-Transferase (GST) variants and its effect on distribution of urinary arsenic species in people exposed to low inorganic arsenic in tap water: An exploratory study. Arch. Environ. Occup. Health. 2010;65:140–147. doi: 10.1080/19338240903390354. - DOI - PubMed
    1. Sun H.J., Rathinasabapathi B., Wu B., Luo J., Pu L.P., Ma L.Q. Arsenic and selenium toxicity and their interactive effects in humans. Environ. Int. 2014;69:148–158. doi: 10.1016/j.envint.2014.04.019. - DOI - PubMed
    1. IARC (International Agency for Research on Cancer) Some drinking-water disinfectants and contaminants, including arsenic, IARC. Monogr. Eval. Carcinog. Risks Hum. 2004;84:1–477. - PMC - PubMed
    1. WHO (World Health Organization) Arsenic in Drinking-water: Background document for development of WHO Guidelines for Drinking-water Quality. WHO Press, World Health Organization; Geneva, Switzerland: 2011.
-