Developmentally restricted genetic determinants of human arsenic metabolism: Association between urinary methylated arsenic and CYT19 polymorphisms in children

Maria Mercedes Meza, Lizhi Yu, Yelitza Y. Rodriguez, Mischa Guild, David Thompson, A. Jay Gandolfi, Walter T. Klimecki

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)775-781
Number of pages7
JournalEnvironmental health perspectives
Volume113
Issue number6
DOIs
StatePublished - Jun 2005

Keywords

  • Arsenic metabolism
  • CYT19
  • GSTO
  • Genetic association
  • PNP
  • Pharmacogenetics
  • Polymorphism
  • SNP

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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