Globally, millions of persons are at risk for the adverse effects of arsenic due to exposure to inorganic arsenic from drinking water. Humans metabolize and eliminate arsenic through oxidative methylation and subsequent urinary excretion. Within a given population, individuals differ in the quantity and the distribution of the various metabolites (i.e. As3+, As5+, monomethyl arsenic(MMA), dimethyl arsenic (DMA)) excreted in urine. This variation may be affected by many factors, but the existence of genetic determinants has been strongly suggested. The purpose of this project is to study the genetic basis of variability in human metabolism of arsenic. We followed up two established cohorts: one is composed of long-term residents from the black foot disease-endemic area of southwestern Taiwan and the other from a nearby area where the arsenic exposure level is considered low. We analyzed the distribution in urine of total arsenic and arsenic metabolites and found substantial differences between two cohorts. Compared with the control group, the cohort from the endemic area had higher percentage of inorganic arsenic and MMA,but lower percentage of DMA in urine. We also analyzed the association between arsenic metabolism and polymorphisms of two human glutathione transfer as eomega genes (GSTO1 and GSTO2), which catalyze there duction of MMA(V), a rate-limiting reaction in the biotransformation of inorganic arsenic. No significant association was found between the GSTO1 A140D poly-morphism and urinary arsenic profile, while the GSTO2N142D polymorphism appeared to be related to elevated ratio of DMA to MMA.
