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

Reprod Toxicol. 2016 Jun:61:28-38. doi: 10.1016/j.reprotox.2016.02.017. Epub 2016 Feb 27.

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.

Keywords: AS3MT; Arsenic; Birth outcomes; Genotype; Prenatal exposure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Arsenic / metabolism*
  • Arsenic / urine
  • Female
  • Genotype
  • Humans
  • Infant, Newborn
  • Male
  • Methyltransferases / genetics*
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Pregnancy Outcome
  • Risk Assessment
  • Sex Factors
  • Young Adult

Substances

  • Methyltransferases
  • AS3MT protein, human
  • Arsenic