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

Gardner, Renee M; Engström, Karin LU ; Bottai, Matteo; Hoque, Waheedul A M; Raqib, Rubhana; Broberg Palmgren, Karin LU and Vahter, Marie (2012) In Pharmacogenetics & Genomics 22(7). p.508-516
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacogenetics & Genomics
volume
22
issue
7
pages
508 - 516
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000305429900004
  • pmid:22547080
  • scopus:84862758605
ISSN
1744-6872
DOI
10.1097/FPC.0b013e3283535d6a
language
English
LU publication?
yes
id
ccf431ab-80b1-44f6-8891-cdbe674b6609 (old id 2609291)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22547080?dopt=Abstract
date added to LUP
2012-06-01 13:18:28
date last changed
2017-05-21 04:31:00
@article{ccf431ab-80b1-44f6-8891-cdbe674b6609,
  abstract     = {OBJECTIVES: <br/><br>
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. <br/><br>
<br/><br>
METHODS: <br/><br>
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. <br/><br>
<br/><br>
CONCLUSION: <br/><br>
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.},
  author       = {Gardner, Renee M and Engström, Karin and Bottai, Matteo and Hoque, Waheedul A M and Raqib, Rubhana and Broberg Palmgren, Karin and Vahter, Marie},
  issn         = {1744-6872},
  language     = {eng},
  number       = {7},
  pages        = {508--516},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Pharmacogenetics & Genomics},
  title        = {Pregnancy and the methyltransferase genotype independently influence the arsenic methylation phenotype.},
  url          = {http://dx.doi.org/10.1097/FPC.0b013e3283535d6a},
  volume       = {22},
  year         = {2012},
}