Abstract

Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways.

Highlights

  • Groundwater pollution by inorganic arsenic (IA) derived from natural origin is a serious issue of public health in the world, especially in developing countries where clean and safe surface water is not available in many places

  • %monomethylated arsenic (MMA)[V] (26.9%) in the urine [16]. These results indicate that genetic polymorphisms of certain enzymes that can metabolize arsenic through methylation pathways may be one of factors associated with the variation of arsenic profiles

  • We have reported the association of arsenic metabolism-single nucleotide polymorphisms (SNPs) in arsenic (+3 oxidation state) methyltransferase (AS3MT) in Vietnamese [17,18,19,20,21]

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Summary

Introduction

Groundwater pollution by inorganic arsenic (IA) derived from natural origin is a serious issue of public health in the world, especially in developing countries where clean and safe surface water is not available in many places In these areas, high arsenic concentrations exceeding the WHO guideline (10 μg/L) for drinking [1] have been reported in the groundwater [2,3,4]. %MMA[V] (26.9%) in the urine [16] These results indicate that genetic polymorphisms of certain enzymes that can metabolize arsenic through methylation pathways may be one of factors associated with the variation of arsenic profiles. Thereafter, the number of publications regarding genetic polymorphisms dependent metabolism and toxicity of arsenic is increasing In this short-review, we address the following three topics: (1) enzymatic processes of arsenic methylation by AS3MT; (2) associations of genetic polymorphisms in AS3MT with variation in arsenic methylation; (3) frequency distributions of genetic polymorphisms in AS3MT at population levels.

Arsenic Methylation by Human AS3MT
Association of Arsenic Methylation with Genotypes in Human AS3MT
In Vitro Studies
Mexico
Argentina
Central Europe
Taiwan
Vietnam
Allele Frequency of SNPs in AS3MT
Findings
Conclusions and Future Perspectives

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