title: Developmentally restricted genetic determinants of human arsenic metabolism: association between urinary methylated arsenic and CYT19 polymorphisms in children.
abstract: We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7-11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18-79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials.
authors.affiliation: Department of Natural Resources, Sonora Institute of Technology (ITSON), Ciudad Obregon, Sonora, Mexico.
authors.forename: Maria Mercedes
authors.initials: MM
authors.lastname: Meza
authors.forename: Lizhi
authors.initials: L
authors.lastname: Yu
authors.forename: Yelitza Y
authors.initials: YY
authors.lastname: Rodriguez
authors.forename: Mischa
authors.initials: M
authors.lastname: Guild
authors.forename: David
authors.initials: D
authors.lastname: Thompson
authors.forename: A Jay
authors.initials: AJ
authors.lastname: Gandolfi
authors.forename: Walter T
authors.initials: WT
authors.lastname: Klimecki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001151:Arsenic / Q000378:metabolism* / Q000652:urine; D001152:Arsenicals / Q000652:urine*; D002648:Child; D004784:Environmental Monitoring; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics*; D008800:Mexico; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics*; D014874:Water Pollutants, Chemical / Q000378:metabolism* / Q000652:urine; D014881:Water Supply
chemical_list: D001152:Arsenicals; D014874:Water Pollutants, Chemical; D008780:Methyltransferases; C505756:AS3MT protein, human; D011683:Purine-Nucleoside Phosphorylase; C490476:GSTO1 protein, human; D005982:Glutathione Transferase; D001151:Arsenic