Role of the Met<inf>287</inf>Thr polymorphism in the AS3MT gene on the metabolic arsenic profile

Alba Hernández, Noel Xamena, Jordi Surrallés, Chandra Sekaran, Hiroshi Tokunaga, Domingo Quinteros, Amadeu Creus, Ricardo Marcos

Research output: Contribution to journalArticleResearchpeer-review

71 Citations (Scopus)

Abstract

Chronic exposure to arsenic involves a biotransformation process leading to the excretion of methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species (AsIII and AsV). Inter-individual variations in arsenic biotransformation have been reported and polymorphisms affecting the genes involved in arsenic biotransformation have been considered as one of the plausible explanations for this variation. Coding and flanking regions of the human arsenic methyltransferase (AS3MT) gene have been analysed in 50 Chilean men exposed to arsenic. Nine polymorphisms were found, including one non-synonymous SNP at exon 9 (Met287Thr) with an allele frequency of 0.14. Other four changes occurred at potentially regulatory regions: a variable number of tandem repeats (VNTR) at the 5′-untranslated region (UTR5′), a G/C substitution at the promoter region, a GC/AT substitution inside the VNTR, and a G/A substitution at the 3′-untranslated region (UTR3′). The rest of polymorphisms were located in non-coding regions: a T/G substitution in intron 1, a CTC deletion in intron 2 and a TTT and ATT insertions in intron 5. In addition, the individual urinary arsenic profiles were analysed. Our results indicate that genetic polymorphisms in AS3MT contribute to inter-individual variation in arsenic biotransformation and, therefore, may contribute to inter-individual variations in risk of arsenic toxicity and arsenic carcinogenesis. Individuals with the Met287Thr polymorphism displayed increased arsenic methylation and might be at increased risk for toxic and genotoxic effects of arsenic exposure if, as the classical arsenic metabolic pathway indicates, methylation enhances toxicity. © 2007.
Original languageEnglish
Pages (from-to)80-92
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume637
Issue number1-2
DOIs
Publication statusPublished - 1 Jan 2008

Keywords

  • Arsenic
  • AS3MT gene
  • Met Thr polymorphism 287
  • Metabolic profile

Fingerprint Dive into the research topics of 'Role of the Met<inf>287</inf>Thr polymorphism in the AS3MT gene on the metabolic arsenic profile'. Together they form a unique fingerprint.

Cite this