The role of glutathione transferase polymorphism in susceptibility to disease

Glutathione S-transferases (GSTs) are a superfamily of enzymes that protect normal cells by catalyzing conjugation reactions of electrophylic compounds, including carcinogens, to glutathione. Some GST enzymes possess antioxidant activity against hydroperoxides. The most well characterized cytosolic classes have been named alpha (GSTA), mu (GSTM), pi (GSTP), theta (GSTT) and omega (GSTO). Several types of allelic variation have been identified within these classes, conferring the loss or impaired catalytic activity. The aim of this project is to investigate the role of GST polymorphisms in susceptibility to malignant and non-malignant diseases related to the exposure to environmental agents. In the first phase the role of GST polymorphism in association with tobacco smoking and/or exposure to chemicals will be examined in susceptibility to renal cell carcinoma, upper urinary tract carcinoma and urinary bladder carcinoma. In contrast to extensive investigation of GST polymorphism in relation to malignancy, their role in cardiovascular risk and pathophysiology of atherosclerosis, particularly in relation to tobacco smoking or systemic oxidative stress remains unclear. Concerning cardiovascular diseases, in this project, the role of GST polymorphism in susceptibility to chronic ischemic heart failure will be studied. Besides, the role of variant GST expression will be studied in chronic renal failure, in which cardiovascular complications are the main reason of poor outcome.