title: Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level.
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.
authors.affiliation: *Department of Nutrition, Gillings School of Global Public Health.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biological Sciences College of Sciences, North Carolina State University, North Carolina.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Drobná
authors.affiliation: *Department of Nutrition, Gillings School of Global Public Health.
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.affiliation: *Department of Nutrition, Gillings School of Global Public Health.
authors.forename: Keri
authors.initials: K
authors.lastname: Barron
authors.affiliation: Programa de Maestría en Ciencias en Biotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, México.
authors.forename: Carmen
authors.initials: C
authors.lastname: González-Horta
authors.affiliation: Programa de Maestría en Ciencias en Biotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, México.
authors.forename: Blanca
authors.initials: B
authors.lastname: Sánchez-Ramírez
authors.affiliation: Programa de Maestría en Ciencias en Biotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, México.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ballinas-Casarrubias
authors.affiliation: Colegio de Médicos Cirujanos y Homeópatas del Estado de Chihuahua, A.C.
authors.forename: Roberto Hernández
authors.initials: RH
authors.lastname: Cerón
authors.affiliation: Colegio de Médicos Cirujanos y Homeópatas del Estado de Chihuahua, A.C.
authors.forename: Damián Viniegra
authors.initials: DV
authors.lastname: Morales
authors.affiliation: Colegio de Médicos Cirujanos y Homeópatas del Estado de Chihuahua, A.C.
authors.forename: Francisco A Baeza
authors.initials: FA
authors.lastname: Terrazas
authors.affiliation: Programa de Maestría en Ciencias en Biotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, México.
authors.forename: María C
authors.initials: MC
authors.lastname: Ishida
authors.affiliation: Programa de Maestría en Ciencias en Biotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, México.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Gutiérrez-Torres
authors.affiliation: *Department of Nutrition, Gillings School of Global Public Health.
authors.forename: R Jesse
authors.initials: RJ
authors.lastname: Saunders
authors.affiliation: Department of Biostatistics Gillings School of Global Public Health School of Nursing.
authors.forename: Jamie
authors.initials: J
authors.lastname: Crandell
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health and Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
authors.affiliation: International Agency for Research of Cancer, Monographs Section, Lyon Cedex, France.
authors.forename: Dana
authors.initials: D
authors.lastname: Loomis
authors.affiliation: Facultad de Medicina, Universidad Juárez del Estado de Durango, Gómez Palacio, Durango, México.
authors.forename: Gonzalo G
authors.initials: GG
authors.lastname: García-Vargas
authors.affiliation: **Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México.
authors.forename: Luz M
authors.initials: LM
authors.lastname: Del Razo
authors.affiliation: *Department of Nutrition, Gillings School of Global Public Health.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Stýblo
authors.affiliation: *Department of Nutrition, Gillings School of Global Public Health Carolina Population Center and Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina mmendez@email.unc.edu.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Mendez
mesh_terms: D000328:Adult; D001151:Arsenic / Q000032:analysis / Q000633:toxicity* / Q000652:urine; D003430:Cross-Sectional Studies; D060766:Drinking Water / Q000737:chemistry*; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D060766:Drinking Water; D008780:Methyltransferases; C505756:AS3MT protein, human; D001151:Arsenic
keywords: Arsenic (+3 oxidation state) methyltranserase polymorphism; arsenic; arsenic metabolites; drinking water; methylation capacity.; urinary arsenic