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Maria Mercedes Meza,^1,* Lizhi Yu,^2,* Yelitza Y. Rodriguez,² Mischa Guild,² David Thompson,² A. Jay Gandolfi,³ and Walter T. Klimecki²

¹Department of Natural Resources, Sonora Institute of Technology (ITSON), Ciudad Obregon, Sonora, Mexico; ²Arizona Respiratory Center, and ³Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA

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. Key words: arsenic metabolism, CYT19, genetic association, GSTO, pharmacogenetics, PNP, polymorphism, SNP. Environ Health Perspect 113:775-781 (2005) . doi:10.1289/ehp.7780 available via http://dx.doi.org/ [Online 22 March 2005]

Address correspondence to W.T. Klimecki, Arizona Respiratory Center, University of Arizona, P.O. Box 245030, Tucson, AZ 85724 USA. Telephone: (520) 626-7470. Fax: (520) 626-6970. E-mail: walt@arc.arizona.edu

*These authors contributed equally to the manuscript.

We thank S. Guerra for constructive discussions of this study.

This research was supported by National Institute of Environmental Health Sciences grant 04940. M.M.M. is supported by the Sonora Institute of Technology (ITSON) .

The authors declare they have no competing financial interests.

Received 22 November 2004 ; accepted 22 March 2005.