High arsenic metabolic efficiency in AS3MT287Thr allele carriers.
OBJECTIVE
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 Met(287)Thr (C/T) polymorphism affected the urinary arsenic profile in a Chilean group of men (n=50) occupationally exposed to arsenic.


METHODS
To confirm, the influence of the Met(287)Thr polymorphism in the metabolism of arsenic, a total of 207 Chilean men working at the copper industry were genotyped and their urinary profiles determined.


RESULTS
The results confirm that Met(287)Thr polymorphism does influence arsenic metabolism in this population. Those carriers of the variant ((287)Thr) 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.


CONCLUSIONS
We can conclude that individuals with the (287)Thr variant display increased arsenic methylation; thus, those participants might be at increased risk for the toxic and genotoxic effects of arsenic exposure.
Hernández
Alba
A
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Xamena
Noel
N
Sekaran
Chandra
C
Tokunaga
Hiroshi
H
Sampayo-Reyes
Adriana
A
Quinteros
Domingo
D
Creus
Amadeu
A
Marcos
Ricardo
R
D000328:Adult; D000483:Alleles; D001149:Arsenates / Q000652:urine*; D003300:Copper; D005838:Genotype; D006801:Humans; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008906:Mining; D011110:Polymorphism, Genetic
D001149:Arsenates; D003300:Copper; D008780:Methyltransferases; C505756:AS3MT protein, human; C025657:arsenic acid