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. 2016 Sep;153(1):112-23.
doi: 10.1093/toxsci/kfw112. Epub 2016 Jun 30.

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

Xiaofan Xu  1 , Zuzana Drobná  2 , V Saroja Voruganti  1 , Keri Barron  1 , Carmen González-Horta  3 , Blanca Sánchez-Ramírez  3 , Lourdes Ballinas-Casarrubias  3 , Roberto Hernández Cerón  4 , Damián Viniegra Morales  4 , Francisco A Baeza Terrazas  4 , María C Ishida  3 , Daniela S Gutiérrez-Torres  3 , R Jesse Saunders  1 , Jamie Crandell  5 , Rebecca C Fry  6 , Dana Loomis  7 , Gonzalo G García-Vargas  8 , Luz M Del Razo  9 , Miroslav Stýblo  1 , Michelle A Mendez  10
Affiliations

Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level

Xiaofan Xu et al. Toxicol Sci. 2016 Sep.

Abstract

Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism-and perhaps with susceptibility to iAs-associated disease-may vary in settings with exposure level.

Keywords: Arsenic (+3 oxidation state) methyltranserase polymorphism; arsenic; arsenic metabolites; drinking water; methylation capacity.; urinary arsenic.

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Figures

FIG. 1.
FIG. 1.
Associations between AS3MT variants and urinary arsenic profiles among subjects with higher versus lower water arsenic (As). †P < .10 ‡P < .05 for differences in urinary As profiles associated with having non-referent AS3MT variants genotypes compared with referent genotypes, where referent genotypes were defined as those associated with a higher DMAs% in previous studies. Wild type genotypes, defined based on global genotype frequency reports from the National Center for Biotechnology Information, were underlined. *Indicates interaction (P < .10) for variant X categorical water iAs (>50 vs ≤ 50 ppb). Results come from multiple linear regression models adjusted for age and gender.
FIG. 1.
FIG. 1.
Associations between AS3MT variants and urinary arsenic profiles among subjects with higher versus lower water arsenic (As). †P < .10 ‡P < .05 for differences in urinary As profiles associated with having non-referent AS3MT variants genotypes compared with referent genotypes, where referent genotypes were defined as those associated with a higher DMAs% in previous studies. Wild type genotypes, defined based on global genotype frequency reports from the National Center for Biotechnology Information, were underlined. *Indicates interaction (P < .10) for variant X categorical water iAs (>50 vs ≤ 50 ppb). Results come from multiple linear regression models adjusted for age and gender.
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