title: Pregnancy and the methyltransferase genotype independently influence the arsenic methylation phenotype.
abstract: OBJECTIVE
  The methyltransferase genotype and pregnancy both influence the arsenic metabolism phenotype, but it is unknown whether these factors interact, explaining the drastic changes in the efficiency of arsenic metabolism observed among pregnant women. The aim of this study was to evaluate the relative contribution of the methyltransferase genotype and pregnancy to the arsenic metabolism phenotype.
  
  
  METHODS
  We studied longitudinally the arsenic metabolite pattern in urine (at approximately gestational weeks 8, 14, and 30) of 303 women exposed to arsenic through drinking water and food in rural Bangladesh. Urinary arsenic metabolites were measured by high-performance liquid chromatography-inductively coupled plasma mass spectrometry. Data were available on genotypes for 16 polymorphisms, combined as haplotypes, in three methyltransferases: arsenic(+III)methyltransferase (AS3MT) and DNA-methyltransferases 1a and 3b (DNMT1a and DNMT3b). Changes in the arsenic metabolite pattern over time were evaluated by haplotype using logistic quantile regression.
  
  
  RESULTS
  All four AS3MT haplotypes and all three DNMT1a haplotypes significantly influenced the metabolite pattern in the pregnant women, with consistent effects of genotype over the entire course of pregnancy. No interaction was found between the haplotypes and pregnancy-related changes in the arsenic metabolism phenotype. DNMT3b haplotypes did not significantly influence the metabolite pattern. We observed a pregnancy-attributable decrease of 5.7% in the most risk-associated monomethylated metabolite, methylarsonic acid, whereas changes between 1.6 and 5.3% of methylarsonic acid could be attributed to haplotypes of AS3MT and DNMT1a.
  
  
  CONCLUSIONS
  Independent of the genotype, the efficiency of arsenic methylation increased markedly over the course of pregnancy. The effect of pregnancy on the metabolite pattern during the observational period was greater than the effect of genotype.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Renee M
authors.initials: RM
authors.lastname: Gardner
authors.forename: Karin
authors.initials: K
authors.lastname: Engström
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.forename: Waheedul A M
authors.initials: WA
authors.lastname: Hoque
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.forename: Karin
authors.initials: K
authors.lastname: Broberg
authors.forename: Marie
authors.initials: M
authors.lastname: Vahter
mesh_terms: D000293:Adolescent; D000328:Adult; D001151:Arsenic / Q000737:chemistry* / Q000378:metabolism; D001152:Arsenicals / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy / Q000378:metabolism*; D000097584:DNA Methyltransferase 3B
chemical_list: D001151:Arsenic; D001152:Arsenicals; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D008780:Methyltransferases; D000097584:DNA Methyltransferase 3B; C505756:AS3MT protein, human; C020300:monomethylarsonic acid