title: Analysis of maternal polymorphisms in arsenic (+3 oxidation state)-methyltransferase AS3MT and fetal sex in relation to arsenic metabolism and infant birth outcomes: Implications for risk analysis.
abstract: Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the metabolism of inorganic arsenic (iAs). Polymorphisms of AS3MT influence adverse health effects in adults, but little is known about their role in iAs metabolism in pregnant women and infants. The relationships between seven single nucleotide polymorphisms (SNPs) in AS3MT and urinary concentrations of iAs and its methylated metabolites were assessed in mother-infant pairs of the Biomarkers of Exposure to ARsenic (BEAR) cohort. Maternal alleles for five of the seven SNPs (rs7085104, rs3740400, rs3740393, rs3740390, and rs1046778) were associated with urinary concentrations of iAs metabolites, and alleles for one SNP (rs3740393) were associated with birth outcomes/measures. These associations were strongly dependent upon the male sex of the fetus but independent of fetal genotype for AS3MT. These data highlight a potential sex-dependence of the relationships among maternal genotype, iAs metabolism and infant health outcomes.
authors.affiliation: Department of Biological Sciences, North Carolina State University, NC 27695, United States.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Drobná
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Martin
authors.affiliation: Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Kyung Su
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Smeester
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Paige
authors.initials: P
authors.lastname: Bommarito
authors.affiliation: Facultad de Medicina, Universidad Juarez del Estado de Durango, Gómez Palacio, Durango, Mexico.
authors.forename: Marisela
authors.initials: M
authors.lastname: Rubio-Andrade
authors.affiliation: Facultad de Medicina, Universidad Juarez del Estado de Durango, Gómez Palacio, Durango, Mexico.
authors.forename: Gonzalo G
authors.initials: GG
authors.lastname: García-Vargas
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Stýblo
authors.affiliation: Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States. Electronic address: rfry@unc.edu.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
mesh_terms: D000293:Adolescent; D000328:Adult; D001151:Arsenic / Q000378:metabolism* / Q000652:urine; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome; D018570:Risk Assessment; D012737:Sex Factors; D055815:Young Adult
chemical_list: D008780:Methyltransferases; C505756:AS3MT protein, human; D001151:Arsenic
keywords: AS3MT; Arsenic; Birth outcomes; Genotype; Prenatal exposure