Citation
Xu, Xiaofan; Drobná, Zuzana; Voruganti, V. Saroja; Barron, Keri; González-Horta, Carmen; Sánchez-Ramirez, Blanca; Ballinas-Casarrubias, Lourdes; Hernández Cerón, Roberto; Viniegra Morales, Damian; & Baeza Terrazas, Francisco A., et al. (2016). Association between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level. Toxicological Sciences, 153(1), 112-123. PMCID: PMC5808745Abstract
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 a parts per thousand currency sign50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures a parts per thousand currency sign50 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.URL
http://dx.doi.org/10.1093/toxsci/kfw112Reference Type
Journal ArticleYear Published
2016Journal Title
Toxicological SciencesAuthor(s)
Xu, XiaofanDrobná, Zuzana
Voruganti, V. Saroja
Barron, Keri
González-Horta, Carmen
Sánchez-Ramirez, Blanca
Ballinas-Casarrubias, Lourdes
Hernández Cerón, Roberto
Viniegra Morales, Damian
Baeza Terrazas, Francisco A.
Ishida, María C.
Gutiérrez-Torres, Daniela S.
Saunders, R. Jesse
Crandell, Jamie L.
Fry, Rebecca C.
Loomis, Dana P.
García-Vargas, Gonzalo G.
Del Razo, Luz M.
Stýblo, Miroslav
Mendez, Michelle A.