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Pregnancy and the methyltransferase genotype independently influence the arsenic methylation phenotype.

Abstract：

OBJECTIVES: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. CONCLUSION: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.

journal_name

Pharmacogenet Genomics

journal_title

Pharmacogenetics and genomics

authors

Gardner RM,Engström K,Bottai M,Hoque WA,Raqib R,Broberg K,Vahter M

doi

10.1097/FPC.0b013e3283535d6a

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

508-16

issue

eissn

1744-6872

issn

1744-6880

journal_volume

pub_type

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Pregnancy and the methyltransferase genotype independently influence the arsenic methylation phenotype.