Serum gamma-glutamyltransferase, oxidized LDL and mortality in the elderly

  • Belinda SpotoEmail author
  • Graziella D’Arrigo
  • Giovanni Tripepi
  • Davide Bolignano
  • Carmine Zoccali
Short Communication



Serum gamma-glutamyltransferase (GGT) is a liver enzyme involved in the metabolism of glutathione (GSH), a major antioxidant in humans. GGT is a risk factor for mortality in young and middle-aged individuals but this association has been poorly investigated in the elderly.


We studied the relationship between GGT and all-cause mortality and tested whether oxidized low-density lipoproteins (oxLDL) modify this association in a cohort of 1038 elderly individuals.


During the observation time (median 9 years), 401 individuals died. In a Cox regression model adjusting for potential confounders, GGT was an independent risk factor for all-cause mortality [HR (20U/L increase in serum GGT): 1.11, 95% CI 1.02–1.21, P = 0.02]. Furthermore, increasing levels of oxLDL amplified the risk excess for all-cause mortality associated with GGT (P for the effect modification = 0.003).


In the elderly, serum GGT is an independent risk factor for all-cause mortality and circulating oxLDL amplify the magnitude of this association.


GGT Mortality Elderly oxLDL 



This work was supported by the National Research Council of Italy (CNR), Research Project “Aging: molecular and technological innovations for improving the health of the elderly population” (Prot. MIUR 2867 25.11.2011). The funding of the study complies with Ethical Standards.

Compliance with ethical standards

Conflict of interest

All the authors declare no conflict of interest.

Ethical approval

The InCHIANTI study protocol met the criteria outlined in the Declaration of Helsinki and the Italian National Research Council on Aging ethics committee approved the study protocol in September 1998.

Informed consent

Written informed consent was obtained from each participant by the InCHIANTI investigators.


  1. 1.
    Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292:R18–R36CrossRefGoogle Scholar
  2. 2.
    Whitfield JB (2001) Gamma glutamyl transferase. Crit Rev Clin Lab Sci 38:263–355CrossRefGoogle Scholar
  3. 3.
    Huseby NE (1982) Multiple forms of serum gamma-glutamyltransferase. Association of the enzyme with lipoproteins. Clin Chim Acta 124:103–112CrossRefGoogle Scholar
  4. 4.
    Kunutsor SK, Apekey TA, Seddoh D et al (2014) Liver enzymes and risk of all-cause mortality in general populations: a systematic review and meta-analysis. Int J Epidemiol 43:187–201CrossRefGoogle Scholar
  5. 5.
    Long Y, Zeng F, Shi J et al (2014) Gamma-glutamyltransferase predicts increased risk of mortality: a systematic review and meta-analysis of prospective observational studies. Free Radic Res 48:716–728CrossRefGoogle Scholar
  6. 6.
    Lee DH, Blomhoff R, Jacobs DR Jr (2004) Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic Res 38:535–539CrossRefGoogle Scholar
  7. 7.
    Paolicchi A, Emdin M, Passino C et al (2006) Beta-lipoprotein- and LDL-associated serum gamma-glutamyltransferase in patients with coronary atherosclerosis. Atherosclerosis. 186:80–85CrossRefGoogle Scholar
  8. 8.
    Paolicchi A, Minotti G, Tonarelli P et al (1999) Gamma-glutamyl transpeptidase-dependent iron reduction and LDL oxidation–a potential mechanism in atherosclerosis. J Investig Med 47:151–160PubMedGoogle Scholar
  9. 9.
    Paolicchi A, Emdin M, Ghliozeni E et al (2004) Images in cardiovascular medicine@ Human atherosclerotic plaques contain gamma-glutamyl transpeptidase enzyme activity. Circulation 109:1440CrossRefGoogle Scholar
  10. 10.
    Loomba R, Doycheva I, Bettencourt R et al (2013) Serum γ-glutamyltranspeptidase predicts all-cause, cardiovascular and liver mortality in older adults. J Clin Exp Hepatol 3:4–11CrossRefGoogle Scholar
  11. 11.
    Wannamethee G, Ebrahim S, Shaper AG (1995) Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes. Am J Epidemiol 142:699–708CrossRefGoogle Scholar
  12. 12.
    Fraser A, Thinggaard M, Christensen K et al (2009) Alanine aminotransferase, gamma-glutamyltransferase (GGT) and all-cause mortality: results from a population-based Danish twins study alanine aminotransferase, GGT and mortality in elderly twins. Liver Int 29:1494–1499CrossRefGoogle Scholar
  13. 13.
    Ferrucci L, Bandinelli S, Benvenuti E et al (2000) Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiology and geriatric practice in the InCHIANTI study. J Am Geriatr Soc 48:1618–1625CrossRefGoogle Scholar
  14. 14.
    Austin PC, Lee DS, Fine JP (2016) Introduction to the analysis of survival data in the presence of competing risks. Circulation 133:601–609CrossRefGoogle Scholar
  15. 15.
    Buja A, Scafato E, Sergi G, ILSA Working Group et al (2010) Alcohol consumption and metabolic syndrome in the elderly: results from the Italian longitudinal study on aging. Eur J Clin Nutr 64:297–307CrossRefGoogle Scholar
  16. 16.
    Vanni E, Bugianesi E, Kotronen A et al (2010) From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis. 42:320–330CrossRefGoogle Scholar
  17. 17.
    Drozdz R, Parmentier C, Hachad H et al (1998) gamma-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med 25:786–792CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.National Council of Research, Institute of Clinical Physiology (CNR-IFC)Reggio CalabriaItaly

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