The Human Genetics of Arsenic Transformation

Figure shows arsenic biotransformation pathway.

Background
Arsenic biotransformation appears to have a considerable degree of inter-individual variability that has the characteristics of being heritably determined, suggested by a number of studies, including reports of familial aggregation of urinary arsenic metabolite levels. Understanding the metabolism of arsenic is a prerequisite to understanding its toxicological effects in humans.

Goal
To fully characterize the genetic variability of all known genes involved in arsenic biotransformation in a diverse group of ethnically defined, globally collected human samples of arsenic-exposed individuals.

Objectives
1. To conduct a large genetic association study with the aim of relating individual variation in arsenic metabolism, measured in two complementary ways-enzymatic activity and urinary metabolite levels, to variations in the DNA sequence of candidate genes involved in arsenic metabolism, including GSTO1-1, PNP, and CYT19.

2. To express variant isoforms of candidate gene products and characterize their biochemical activity to complement the genetic associations with mechanistic information.

3. To identify new arsenic biotransformation pathway members.

Contact
Vasken H. Aposhian
aposhian@u.arizona.edu
(520) 621-7565