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Individual variations in inorganic arsenic metabolism associated with AS3MT genetic polymorphisms
Tetsuro Agusa1, Junko Fujihara, Haruo Takeshita
1Department of Legal Medicine, Faculty of Medicine, Shimane University, Enya 89-1, Izumo 693-8501, Japan; E-Mails: ax@med.shimane-u.ac.jp or ax@agr.ehime-u.ac.jp (T.A.); jfujihara@med.shimane-u.ac.jp (J.F.); htakeshi@med.shimane-u.ac.jp (H.T.).
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.
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