Gamma GT (GGT) and mortality

• glycoprotein gamma glutamyltransferase (GGT) is located on membranes of cells with high secretory or absorptive activities, such as in liver, kidney, pancreas, intestine, heart, brain, and prostate, but not in bone or erythrocytes
  • serum GGT is significantly increased in hepatobiliary diseases, with highest concentrations in cholestatic conditions
    
    
• several studies have shown its association with morbidity and mortality from other causes, especially cardiovascular disease (CVD) (1,2,3,4,5,6)
  
  
  • also been important advances in the definition of the associations of serum GGT with type 2 diabetes and with stroke
    
    
  • serum GGT concentrations are associated with increased risk of myocardial infarction and cardiac death
    
    
  • an independent prognostic role of GGT for all-cause mortality in males has also been reported

GGT is associated with mortality in both men and women, especially in patients younger than 30 years, and even high-normal GGT is a risk factor for all-cause mortality (4)

A cohort study in the elderly population revealed GGT was associated with increased CVD mortality as well as increased all-cause mortality (5).

Notes:

• GGT participates in the metabolism of cellular glutathione, and serum GGT, within its normal interval, has been proposed as a marker of oxidative stress
  • presence of GGT enzyme activity has been demonstrated within coronary atherosclerotic plaques from endoarterectomy specimens
    • oxidative stress mediated by GGT could thus play a relevant role in the evolution of atherosclerotic plaque and its instabilization
    • a strong relation of serum GGT to CRP has been described, further pointing to the role of oxidative stress as a key component of many reactions associated with chronic inflammation
      
      
• therapeutic measures for lowering GGT
  • in addition to known measures, such as avoidance of alcohol consumption and hepatotoxic drugs, a number of other variables, such as coffee consumption, weight loss, smoking cessation, and changes in nutrition, have been described to be beneficial in reduction of serum GGT

Reference:

• Goldberg DM. Structural, functional, and clinical aspects of gamma-glutamyltransferase. CRC Crit Rev Clin Lab Sci 1980;12:1-58
• Brenner H, Rothenbacher D, Arndt V, Schuberth S, Fraisse E, Fliedner TM. Distribution, determinants, and prognostic value of gamma-glutamyltransferase for all-cause mortality in a cohort of construction workers from southern Germany. Prev Med 1997;26:305-310
• Wannamethee G, Ebrahim S, Shaper AG. Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes. Am J Epidemiol 1995;142:699-708
• Kazemi-Shirazi L et al.Gamma glutamyltransferase and long-term survival: is it just the liver? Clin Chem. 2007 May;53(5):940-6.
• Koehler EM et al. Serum liver enzymes are associated with all-cause mortality in an elderly population.Liver Int. 2013 Sep 11. doi: 10.1111/liv.12311.
• Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the united states population. Gastroenterology 2009; 136 477-85 e11.