High arsenic metabolic efficiency in AS3MT 287Thr allele carriers

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Abstract
Epidemiological data indicate the existence of wide interindividual differences in arsenic metabolism. It has recently been shown that arsenic(III)methyltransferase (AS3MT) enzyme catalyses the methylation of arsenite and monomethylarsonous acid (MMA). Thus, genetic variations in the AS3MT gene could explain, at least partly, the interindividual variation in the response to arsenic exposure. In an earlier study, we have demonstrated that the AS3MT Met287Thr (C/T) polymorphism affected the urinary arsenic profile in a Chilean group of men (n=50) occupationally exposed to arsenic. To confirm, the influence of the Met287Thr polymorphism in the metabolism of arsenic, a total of 207 Chilean men working at the copper industry were genotyped and their urinary profiles determined. The results confirm that Met287Thr polymorphism does influence arsenic metabolism in this population. Those carriers of the variant (287Thr) had a higher methylation efficiency, excreting 4.63% more MMA in urine (P=0.0007) and presenting a 2.98 times higher odd of excreting levels of MMA over the standard (P=0.011) than the participants homozygous for the normal allele. We can conclude that individuals with the 287Thr variant display increased arsenic methylation; thus, those participants might be at increased risk for the toxic and genotoxic effects of arsenic exposure.

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