Association of glutathione S-transferase Ω 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-β), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water

Human exposure to arsenicals is associated with inflammatory-related diseases including different kinds of cancer as well as non-cancerous diseases like neuro-degenerative diseases, atherosclerosis, hypertension, and diabetes. Interindividual susceptibility has been mainly addressed by evaluating the role of genetic polymorphism in metabolic enzymes in inorganic arsenic (iAs) metabolism. Glutathione S-transferase omega 1-1 (GSTO1-1), which had been associated with iAs metabolism, is also known to participate in inflammatory and apoptotic cellular responses. The polymorphism A140D of GSTO1-1 has been not only associated with distinct urinary profile of arsenic metabolites in populations chronically exposed to iAs in drinking water, but also with higher risk of childhood leukemia and lung disease in non-exposed populations, suggesting that GSTO1-1 involvement in other physiologic processes different from toxics metabolism could be more relevant than is thought. We evaluated the association of the presence of A140D and E208K polymorphisms of GSTO1-1 gene with the expression of genes codifying for proteins involved in the inflammatory and apoptotic response in a human population chronically exposed to iAs through drinking water. A140D polymorphism was associated with higher expression of genes codifying for IL-8 and Apaf-1 mainly in heterozygous individuals, while E208K was associated with higher expression of IL-8 and TGF-beta gene, in both cases, the association was independently of iAs exposure level; however, the exposure to iAs increased slightly but significantly the influence of A140D and E208K polymorphisms on such genes expression. These results suggest an important role of GSTO1-1 in the inflammatory response and the apoptotic process and indicate that A140D and E208K polymorphisms could increase the risk of developing inflammatory and apoptosis-related diseases in As-exposed populations.