Are Glutathione S -Transferase Null Genotypes “Null and Void” of Risk for Ischemic Vascular Disease?

Abstract

The major risk factors for cardiovascular disease (CVD) relate to intrinsic changes in cholesterol metabolism or blood pressure regulation or to diseases such as diabetes. In addition, it has been found that chemical and pollutant exposure has adverse effects on cardiovascular health. Although we have known about the harmful effects of smoking on heart disease for a long time, recent research shows that exposure to other environmental pollutants such as ambient air particles, automobile exhaust, and pesticides can also increases CVD risk.1 It is therefore reasonable to expect that CVD risk could be modified by metabolic processes that detoxify foreign chemicals (xenobiotics) or even endogenous toxins (eg, products of lipid peroxidation). The concept that the mechanisms of detoxification regulate disease susceptibility is one of the cornerstones of cancer research; however, only recently have we begun to appreciate the cardiovascular implications of this concept. Article see p 418 For the most part, the relationships between CVD and detoxification mechanisms remain unknown. Glutathione S -transferases (GSTs), however, are one exception. These enzymes catalyze the conjugation of glutathione with electrophilic xenobiotics.2 In Phase II detoxification reactions, they transform xenobiotics into usually less reactive, water-soluble compounds that are excreted in urine or bile. Genetic variations and deletion genotypes of GSTs are relatively prevalent in human populations. Several studies have suggested that variations in GSTs alter CVD risk particularly in smokers, but the data are inconsistent. Some studies report strong interactions between GST genotypes and smoking, whereas others have found no significant association. The current study by Norskov et al,3 published in this issue of Circulation: Cardiovascular Genetics , is the most highly powered epidemiological study to date that investigates the contribution of GSTs to CVD risk specifically for ischemic heart disease (IHD) and cerebrovascular disease. Norskov et al studied the gene …