Evidence map›Paper›PMID 23341986›Full record

Trial reportPloS one2013

Efficient arsenic metabolism--the AS3MT haplotype is associated with DNA methylation and expression of multiple genes around AS3MT.

Karin S Engström, Mohammad Bakhtiar Hossain, Martin Lauss, Sultan Ahmed, Rubhana Raqib, Marie Vahter, Karin Broberg

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Welding Fume Exposure and Epigenetic Alterations: A Systematic Review.International journal of environmental research and public health · 2019
    Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Biomonitoring of inorganic arsenic species in pregnancy.Journal of exposure science & environmental epidemiology · 2023
    Review
  8. Article
  9. Article
  10. Rare, Protein-Altering Variants inEnvironmental health perspectives · 2021
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Transcriptomics in toxicology.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Karin S EngströmSection of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Mohammad Bakhtiar Hossain
Martin Lauss
Sultan Ahmed
Rubhana Raqib
Marie Vahter
Karin Broberg
International Centre for Diarrhoeal Disease Research · BDKarolinska Institutet · SELund University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Arsenic is a very potent toxicant. One major susceptibility factor for arsenic-related toxicity is the efficiency of arsenic metabolism. The efficiency, in turn, is associated with non-coding single nucleotide polymorphisms (SNPs) in the arsenic methyltransferase AS3MT on chromosome 10q24. However, the mechanism of action for these SNPs is not yet clarified. Here, we assessed the influence of genetic variation in AS3MT on DNA methylation and gene expression within 10q24, in people exposed to arsenic in drinking water. DNA was extracted from peripheral blood from women in the Argentinean Andes (N = 103) and from cord blood from new-borns in Bangladesh (N = 127). AS3MT SNPs were analyzed with Sequenom or Taqman assays. Whole genome epigenetic analysis with Infinium HumanMethylation450 BeadChip was performed on bisulphite-treated DNA. Whole genome gene expression analysis was performed with Illumina DirectHyb HumanHT-12 v4.0 on RNA from peripheral blood. Arsenic exposure was assessed by HPLC-ICPMS. In the Argentinean women, the major AS3MT haplotype, associated with more efficient arsenic metabolism, showed increased methylation of AS3MT (p = 10(-6)) and also differential methylation of several other genes within about 800 kilobasepairs: CNNM2 (p<10(-16)), NT5C2 (p<10(-16)), C10orf26 (p = 10(-8)), USMG5 (p = 10(-5)), TRIM8 (p = 10(-4)), and CALHM2 (p = 0.038) (adjusted for multiple comparisons). Similar, but weaker, associations between AS3MT haplotype and DNA methylation in 10q24 were observed in cord blood (Bangladesh). The haplotype-associated altered CpG methylation was correlated with reduced expression of AS3MT and CNNM2 (r(s) = -0.22 to -0.54), and with increased expression of NT5C2 and USMG5 (r(s) = 0.25 to 0.58). Taking other possibly influential variables into account in multivariable linear models did only to a minor extent alter the strength of the associations. In conclusion, the AS3MT haplotype status strongly predicted DNA methylation and gene expression of AS3MT as well as several genes in 10q24. This raises the possibility that several genes in this region are important for arsenic metabolism.

Indexed as

DNA MethylationGene Expression RegulationAdultArsenicChildChromosomes, Human, Pair 10Cohort StudiesCpG IslandsEnvironmental PollutantsEpigenomicsFemaleHaplotypesHumansMaleMethyltransferasesMothersArsenicAS3MT protein, humanEnvironmental PollutantsMethyltransferases

Identifiers

PMID23341986
PMCPMC3544896
OpenAlexW2088546840

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.