What does serum γ-glutamyltransferase tell us as a cardiometabolic risk marker?

γ-glutamyltransferase plays a key role in the synthesis and metabolism of extracellular glutathione, a major antioxidant in several defence mechanisms in the body. γ-glutamyltransferase is affected by environmental and genetic factors, and is raised when there is depletion of glutathione. Hence, it is a marker of oxidative stress. There is robust evidence that γ-glutamyltransferase even when values are within the reference interval is associated with increased cardiovascular and all-cause mortality in both sexes, in normal subjects and subjects with coronary artery disease, in the middle-aged and the elderly after adjusting for confounding factors. γ-glutamyltransferase even within the reference interval is associated with future presentation of type 2 diabetes, and the longitudinal increase in γ-glutamyltransferase activity is associated with increased risk of type 2 diabetes and cardiovascular mortality. γ-glutamyltransferase is associated with cardiovascular risk factors and metabolic syndrome. It has a prognostic value after a previous acute myocardial infarction and may be an indicator of adverse outcome in acute coronary syndromes and other chronic cardiac disorders. There is limited data about γ-glutamyltransferase and any association with peripheral arterial disease and also whether knowing γ-glutamyltransferase activity improves cardiovascular risk prediction beyond conventional risk factors. γ-glutamyltransferase is present in atherosclerotic lesions in the coronary and carotid arteries, and has a prooxidant role leading to the production of reactive oxygen species and atherosclerosis. Current reference intervals for γ-glutamyltransferase are inappropriate and need to be addressed. Some laboratories still use non- International Federation of Clinical Chemistry methods for estimation of γ-glutamyltransferase which are associated with lower results. Such laboratories should review their method and consider changing to the International Federation of Clinical Chemistry method.