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

Abstract

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.

Gamma-glutamyl transferase and cardiovascular disease

“…The gene transcription is controlled by multiple promoters. Related gene sequences that are either nonfunctional or represent pseudogenes are found in chromosomes 18,19, and 20 (6,7). The multiple promoters and the alternative splicing are responsible for diversity of molecular forms and tissue specificity.…”

“…The association of GGT with other morbid conditions is not covered. For detailed information, the reader may refer to recent reviews on these topics (8,17,18).…”

“…GGT is closely associated with established cardiovascular risk factors (which tend to cluster in patients with higher GGT level), metabolic syndrome and insulin resistance (18). Elevated GGT may be a marker of antioxidant inadequacy and of increased oxidative stress (17).…”

Evaluation of gamma glutamyl transferase enzyme level in intensive care patients with sepsis related kidney function disturbance

“…GGT, memelilerde ana hücre içi antioksidanlardan biri olan hücre dışı indirgenmiş glutatyonun hidrolizinden sorumlu olan ve öncül aminoasitlerin daha sonra yeni hücre içi glutatyon sentezi için kullanılmasını sağlayan enzimdir. Hücre içi glutatyon tükenmesi ve bu nedenle GGT, oksidatif stresin bir belirteci olarak değerlendirilir [12]. Klinik pratikte artmış serum GGT konsantrasyonu alkol tüketimi veya karaciğer hastalığının tespitinde kullanılmaktadır [13,14].…”

The relationship between Gamma-Glutamyltransferase activity and atrial fibrillation ın patients with reduced ejection fraction heart failure

“…The presence of one can trigger the other, and coexistence worsens the prognosis. In both conditions, age, hypertension, valvular disease, myocardial infarction, and genetic causes are common risk factors 15 .…”