Table of Contents Author Guidelines Submit a Manuscript
Disease Markers
Volume 2015, Article ID 818570, 18 pages
http://dx.doi.org/10.1155/2015/818570
Review Article

Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk

1Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746, USA
2Iron Disorders Institute, Greenville, SC 29615, USA
3Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA

Received 2 July 2015; Accepted 20 September 2015

Academic Editor: Ralf Lichtinghagen

Copyright © 2015 Gerald Koenig and Stephanie Seneff. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. B. Whitfield, “Gamma glutamyl transferase,” Critical Reviews in Clinical Laboratory Sciences, vol. 38, no. 4, pp. 263–355, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. A public service on clinical lab testing from the laboratory professionals who do the testing, Internet description of GGT provided by Lab Tests Online, 2015, https://labtestsonline.org/understanding/analytes/ggt/tab/test/.
  3. S. Wickham, M. B. West, P. F. Cook, and M. H. Hanigan, “Gamma-glutamyl compounds: substrate specificity of gamma-glutamyl transpeptidase enzymes,” Analytical Biochemistry, vol. 414, no. 2, pp. 208–214, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Corti, T. L. Duarte, C. Giommarelli et al., “Membrane gamma-glutamyl transferase activity promotes iron-dependent oxidative DNA damage in melanoma cells,” Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, vol. 669, no. 1-2, pp. 112–121, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. H. Milnerowicz, R. Bukowski, M. Jabłonowska, M. Ściskalska, and S. Milnerowicz, “The antioxidant profiles, lysosomal and membrane enzymes activity in patients with acute pancreatitis,” Mediators of Inflammation, vol. 2014, Article ID 376518, 9 pages, 2014. View at Publisher · View at Google Scholar
  6. H. Aberkane, J.-F. Stoltz, M.-M. Galteau, and M. Wellman, “Erythrocytes as targets for gamma-glutamyltranspeptidase initiated pro-oxidant reaction,” European Journal of Haematology, vol. 68, no. 5, pp. 262–271, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. G. B. Stefano and R. M. Kream, “Nitric oxide regulation of mitochondrial processes: commonality in medical disorders,” Annals of Transplantation, vol. 20, pp. 402–407, 2015. View at Publisher · View at Google Scholar
  8. M. Sreeram, A. N. Suryakar, and N. H. Dani, “Is gamma-glutamyl transpeptidase a biomarker for oxidative stress in periodontitis?” Journal of Indian Society of Periodontology, vol. 19, no. 2, pp. 150–154, 2015. View at Publisher · View at Google Scholar
  9. D. S. Lee, J. C. Evans, S. J. Robins et al., “Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart study,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 1, pp. 127–133, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. R. Dhingra, P. Gona, T. J. Wang, C. S. Fox, R. B. Dagostino, and R. S. Vasan, “Serum γ-glutamyl transferase and risk of heart failure in the community,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 9, pp. 1855–1860, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. D.-H. Lee, L. M. Steffen, and D. R. Jacobs Jr., “Association between serum γ-glutamyltransferase and dietary factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study,” American Journal of Clinical Nutrition, vol. 79, no. 4, pp. 600–605, 2004. View at Google Scholar · View at Scopus
  12. J. Montonen, H. Boeing, A. Fritsche et al., “Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress,” European Journal of Nutrition, vol. 52, no. 1, pp. 337–345, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. N. M. Pham, W. Zhenjie, M. Morita et al., “Combined effects of coffee consumption and serum γ-glutamyltransferase on serum C-reactive protein in middle-aged and elderly Japanese men and women,” Clinical Chemistry and Laboratory Medicine, vol. 49, no. 10, pp. 1661–1667, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Sartori, S. Andorno, A. Rossini et al., “Phlebotomy improves histology in chronic hepatitis C males with mild iron overload,” World Journal of Gastroenterology, vol. 16, no. 5, pp. 596–602, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Kazemi-Shirazi, G. Endler, S. Winkler, T. Schickbauer, O. Wagner, and C. Marsik, “Gamma glutamyltransferase and long-term survival: is it just the liver?” Clinical Chemistry, vol. 53, no. 5, pp. 940–946, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. D.-H. Lee, K. Silventoinen, G. Hu et al., “Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28 838 middle-aged men and women,” European Heart Journal, vol. 27, no. 18, pp. 2170–2176, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. C. E. Ruhl and J. E. Everhart, “Elevated serum alanine aminotransferase and γ-glutamyltransferase and mortality in the United States population,” Gastroenterology, vol. 136, no. 2, pp. 477–485, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. E. Ruttmann, L. J. Brant, H. Concin, G. Diem, K. Rapp, and H. Ulmer, “γ-Glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163 944 Austrian adults,” Circulation, vol. 112, no. 14, pp. 2130–2137, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Postorino, C. Marino, G. Tripepi, and C. Zoccali, “Gammaglutamyltransferase in ESRD as a predictor of all-cause and cardiovascular mortality: another facet of oxidative stress burden,” Kidney International, vol. 74, no. 111, pp. S64–S66, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Himmelfarb, P. Stenvinkel, T. A. Ikizler, and R. M. Hakim, “The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia,” Kidney International, vol. 62, no. 5, pp. 1524–1538, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. G. R. Buettner and B. A. Jurkiewicz, “Catalytic metals, ascorbate and free radicals: combinations to avoid,” Radiation Research, vol. 145, no. 5, pp. 532–541, 1996. View at Publisher · View at Google Scholar · View at Scopus
  22. A. M. Strasak, K. Rapp, L. J. Brant et al., “Association of γ-glutamyltransferase and risk of cancer incidence in men: a prospective study,” Cancer Research, vol. 68, no. 10, pp. 3970–3977, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. A. M. Strasak, R. M. Pfeiffer, J. Klenk et al., “Prospective study of the association of gamma-glutamyltransferase with cancer incidence in women,” International Journal of Cancer, vol. 123, no. 8, pp. 1902–1906, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Mok, D. K. Son, Y. Y. Duk, S. H. Jee, and J. M. Samet, “γ-Glutamyltransferase and cancer risk: the Korean cancer prevention study,” International Journal of Cance, 2015. View at Publisher · View at Google Scholar
  25. G. Lum, “Gamma-glutamyl transpeptidase in cancer diagnosis,” Annals of Clinical & Laboratory Science, vol. 4, no. 1, pp. 13–18, 1974. View at Google Scholar · View at Scopus
  26. J.-S. Lim, J.-H. Yang, B.-Y. Chun, S. Kam, D. R. Jacobs Jr., and D.-H. Lee, “Is serum γ-glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress?” Free Radical Biology and Medicine, vol. 37, no. 7, pp. 1018–1023, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. D.-H. Lee, M. D. Gross, and D. R. Jacobs Jr., “Association of serum carotenoids and tocopherols with γ-glutamyltransferase: the Cardiovascular Risk Development in Young Adults (CARDIA) study,” Clinical Chemistry, vol. 50, no. 3, pp. 582–588, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. D.-H. Lee and D. R. Jacobs Jr., “Association between serum gamma-glutamyltransferase and C-reactive protein,” Atherosclerosis, vol. 178, no. 2, pp. 327–330, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. K.-N. Kim, K.-M. Kim, D.-J. Lee, and N.-S. Joo, “Serum gamma-glutamyltransferase concentration correlates with Framingham risk score in Koreans,” Journal of Korean Medical Science, vol. 26, no. 10, pp. 1305–1309, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. A. I. Atar, O. C. Yilmaz, K. Akin, Y. Selcoki, O. Er, and B. Eryonucu, “Association between gamma-glutamyltransferase and coronary artery calcification,” International Journal of Cardiology, vol. 167, no. 4, pp. 1264–1267, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. W. Lee, J.-H. Ryoo, B. S. Suh, J. Lee, and J. Kim, “Association of coronary artery calcification and serum gamma-glutamyl transferase in Korean,” Atherosclerosis, vol. 226, no. 1, pp. 269–274, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. O. Celik, H. A. Cakmak, S. Satilmis et al., “The relationship between gamma-glutamyl transferase levels and coronary plaque burdens and plaque structures in young adults with coronary atherosclerosis,” Clinical Cardiology, vol. 37, no. 9, pp. 552–557, 2014. View at Publisher · View at Google Scholar · View at Scopus
  33. D.-H. Lee and D. R. Jacobs, “Is serum γ-glutamyltransferase an exposure marker of xenobiotics? Empirical evidence with polycylic aromatic hydrocarbon,” Clinical Chemistry and Laboratory Medicine, vol. 47, no. 7, pp. 860–862, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. D.-H. Lee, M. W. Steffes, and D. R. Jacobs Jr., “Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?” Diabetologia, vol. 51, no. 3, pp. 402–407, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. S. K. Venn-Watson, C. Parry, M. Baird et al., “Increased dietary intake of saturated fatty acid heptadecanoic acid (C17:0) associated with decreasing ferritin and alleviated metabolic syndrome in dolphins,” PLOS ONE, vol. 10, no. 7, Article ID e0132117, 2015. View at Publisher · View at Google Scholar
  36. Science Daily, 2015, http://www.sciencedaily.com/releases/2015/07/150722144627.htm.
  37. S. P. Johnson, S. K. Venn-Watson, S. E. Cassle, C. R. Smith, E. D. Jensen, and S. H. Ridgway, “Use of phlebotomy treatment in Atlantic bottlenose dolphins with iron overload,” Journal of the American Veterinary Medical Association, vol. 235, no. 2, pp. 194–200, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. L. Valenti, A. L. Fracanzani, P. Dongiovanni et al., “A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia,” World Journal of Gastroenterology, vol. 20, no. 11, pp. 3002–3010, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. B. Jenkins, J. A. West, and A. Koulman, “A review of odd-chain fatty acid metabolism and the role of pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) in health and disease,” Molecules, vol. 20, no. 2, pp. 2425–2444, 2015. View at Publisher · View at Google Scholar · View at Scopus
  40. M. A. Pereira, D. R. Jacobs Jr., L. Van Horn, M. L. Slattery, A. I. Kartashov, and D. S. Ludwig, “Dairy consumption, obesity, and the insulin resistance syndrome in young adults: the CARDIA study,” The Journal of the American Medical Association, vol. 287, no. 16, pp. 2081–2089, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Y. Abdalla, M. Fawzi, S. R. Al-Maloul, N. El-Banna, R. F. Tayyem, and I. M. Ahmad, “Increased oxidative stress and iron overload in Jordanian β-thalassemic children,” Hemoglobin, vol. 35, no. 1, pp. 67–79, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. H. F. J. Hendriks, E. J. Brink, G. W. Meijer, H. M. G. Princen, and F. Y. Ntanios, “Safety of long-term consumption of plant sterol esters-enriched spread,” European Journal of Clinical Nutrition, vol. 57, no. 5, pp. 681–692, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. D.-H. Lee, J.-S. Lim, K. Song, Y. Boo, and D. R. Jacobs Jr., “Graded associations of blood lead and urinary cadmium concentrations with oxidative-stress-related markers in the U.S. population: results from the third National Health and Nutrition Examination Survey,” Environmental Health Perspectives, vol. 114, no. 3, pp. 350–354, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. A. K. McElroy, B. R. Erickson, T. D. Flietstra et al., “Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome,” The Journal of Infectious Diseases, vol. 210, no. 4, pp. 558–566, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. T. K. Warren, J. C. Trefry, S. T. Marko et al., “Euthanasia assessment in ebola virus infected nonhuman primates,” Viruses, vol. 6, no. 11, pp. 4666–4682, 2014. View at Publisher · View at Google Scholar · View at Scopus
  46. F. A. Badria, A. S. Ibrahim, A. F. Badria, A. A. Elmarakby, and G. Li Volti, “Curcumin attenuates iron accumulation and oxidative stress in the liver and spleen of chronic iron-overloaded rats,” PLOS ONE, vol. 10, no. 7, Article ID e0134156, 2015. View at Publisher · View at Google Scholar
  47. N. Kamalakkannan, R. Rukkumani, P. S. Varma, P. Viswanathan, K. N. Rajasekharan, and V. P. Menon, “Comparative effects of curcumin and an analogue of curcumin in carbon tetrachloride-induced hepatotoxicity in rats,” Basic & Clinical Pharmacology & Toxicology, vol. 97, no. 1, pp. 15–21, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. P. F. Baillie-Hamilton, “Chemical toxins: a hypothesis to explain the global obesity epidemic,” The Journal of Alternative and Complementary Medicine, vol. 8, no. 2, pp. 185–192, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. J. Suh, S. K. Park, J.-M. Choi, and J.-H. Ryoo, “The clinical importance of serum γ-glutamyltransferase level as an early predictor of obesity development in Korean men,” Atherosclerosis, vol. 227, no. 2, pp. 437–441, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Alam, S. M. Noor-E-Alam, Z. R. Chowdhury, M. Alam, and J. Kabir, “Nonalcoholic steatohepatitis in nonalcoholic fatty liver disease patients of Bangladesh,” World Journal of Hepatology, vol. 5, no. 5, pp. 281–287, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. S. K. Park, W. J. Choi, C.-M. Oh, J. Kim, H. Shin, and J.-H. Ryoo, “Association between serum ferritin levels and the incidence of obesity in Korean men: a prospective cohort study,” Endocrine Journal, vol. 61, no. 3, pp. 215–224, 2014. View at Publisher · View at Google Scholar · View at Scopus
  52. S. K. Park, J.-H. Ryoo, M.-G. Kim, and J.-Y. Shin, “Association of serum ferritin and the development of metabolic syndrome in middle-aged Korean men: a 5-year follow-up study,” Diabetes Care, vol. 35, no. 12, pp. 2521–2526, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. B.-S. Suh, “The association between serum gamma-glutamyltransferase within normal levels and metabolic syndrome in office workers: a 4-year follow-up study,” Korean Journal of Family Medicine, vol. 33, no. 1, pp. 51–58, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. G. Targher, M. Franchini, M. Montagnana, and G. Lippi, “The role of iron in diabetes and its complications: reponse to Swaminathan et al,” Diabetes Care, vol. 30, no. 12, article e132, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Swaminathan, V. A. Fonseca, M. G. Alam, and S. V. Shah, “The role of iron in diabetes and its complications,” Diabetes Care, vol. 30, no. 7, pp. 1926–1933, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. D. Wei, T. Chen, J. Li et al., “Association of serum gamma-glutamyl transferase and ferritin with the metabolic syndrome,” Journal of Diabetes Research, vol. 2015, Article ID 741731, 10 pages, 2015. View at Publisher · View at Google Scholar
  57. S. M. Grundy, J. I. Cleeman, S. R. Daniels et al., “Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement,” Circulation, vol. 112, no. 17, pp. 2735–2752, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Chun, S. K. Park, and J.-H. Ryoo, “Association of serum γ-glutamyltransferase level and incident prehypertension in Korean men,” Journal of Korean medical science, vol. 28, no. 11, pp. 1603–1608, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. J.-H. Ryoo, C.-M. Oh, H. S. Kim, S. K. Park, and J.-M. Choi, “Clinical association between serum γ-glutamyltransferase levels and the development of insulin resistance in Korean men: a 5-year follow-up study,” Diabetic Medicine, vol. 31, no. 4, pp. 455–461, 2014. View at Publisher · View at Google Scholar · View at Scopus
  60. S. B. Sridhar, F. Xu, J. Darbinian, C. P. Quesenberry, A. Ferrara, and M. M. Hedderson, “Pregravid liver enzyme levels and risk of gestational diabetes mellitus during a subsequent pregnancy,” Diabetes Care, vol. 37, no. 7, pp. 1878–1884, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. T. Zhuang, H. Han, and Z. Yang, “Iron, oxidative stress and gestational diabetes,” Nutrients, vol. 6, no. 9, pp. 3968–3980, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. D.-H. Lee, R. Blomhoff, and D. R. Jacobs Jr., “Is serum gamma glutamyltransferase a marker of oxidative stress?” Free Radical Research, vol. 38, no. 6, pp. 535–539, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Zein, S. Rachidi, S. Awada et al., “High iron level in early pregnancy increased glucose intolerance,” Journal of Trace Elements in Medicine and Biology, vol. 30, pp. 220–225, 2015. View at Publisher · View at Google Scholar
  64. P. Javadian, S. Alimohamadi, M. H. Gharedaghi, and S. Hantoushzadeh, “Gestational diabetes mellitus and iron supplement; effects on pregnancy outcome,” Acta Medica Iranica, vol. 52, no. 5, pp. 385–389, 2014. View at Google Scholar · View at Scopus
  65. F. N. Amiri, Z. Basirat, S. Omidvar, M. Sharbatdaran, K. H. Tilaki, and M. Pouramir, “Comparison of the serum iron, ferritin levels and total iron-binding capacity between pregnant women with and without gestational diabetes,” Journal of Natural Science, Biology and Medicine, vol. 4, no. 2, pp. 302–305, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. M. Sartori, S. Andorno, A. Rossini et al., “A case-control histological study on the effects of phlebotomy in patients with chronic hepatitis C,” European Journal of Gastroenterology and Hepatology, vol. 23, no. 12, pp. 1178–1184, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. R. Rukkumani, K. Aruna, P. S. Varma, K. N. Rajasekaran, and V. P. Menon, “Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress,” Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 2, pp. 274–283, 2004. View at Google Scholar · View at Scopus
  68. S. Minear, A. F. O'Donnell, A. Ballew et al., “Curcumin inhibits growth of saccharomyces cerevisiae through iron chelation,” Eukaryotic Cell, vol. 10, no. 11, pp. 1574–1581, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Chuengsamarn, S. Rattanamongkolgul, R. Luechapudiporn, C. Phisalaphong, and S. Jirawatnotai, “Curcumin extract for prevention of type 2 diabetes,” Diabetes Care, vol. 35, no. 11, pp. 2121–2127, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Palmier, A. Dixon, and B. Lanzarth, Leading Contributors to Mortality Risk in Life Insurance Applicants, Smalltalk Issue 38, Society of Actuaries, Schaumburg, Ill, USA, 2012.
  71. J. Palmier and B. J. Lanzrath, “Laboratory and biometric predictors of cancer-related mortality in an insured population,” Journal of Insurance Medicine, vol. 43, no. 3, pp. 162–168, 2012. View at Google Scholar · View at Scopus
  72. E. E. Calle, C. Rodriguez, K. Walker-Thurmond, and M. J. Thun, “Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults,” The New England Journal of Medicine, vol. 348, no. 17, pp. 1625–1638, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. M. C. Gonzalez, C. A. Pastore, S. P. Orlandi, and S. B. Heymsfield, “Obesity paradox in cancer: new insights provided by body composition,” The American Journal of Clinical Nutrition, vol. 99, no. 5, pp. 999–1005, 2014. View at Publisher · View at Google Scholar · View at Scopus
  74. W. Nie, Y. Zhang, S. H. Jee, K. J. Jung, B. Li, and Q. Xiu, “Obesity survival paradox in pneumonia: a meta-analysis,” BMC Medicine, vol. 12, no. 1, article 61, 2014. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. Pan and R. T. Jackson, “Insights into the ethnic differences in serum ferritin between black and white US adult men,” American Journal of Human Biology, vol. 20, no. 4, pp. 406–416, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. L. R. Zacharski, D. L. Ornstein, S. Woloshin, and L. M. Schwartz, “Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data,” American Heart Journal, vol. 140, no. 1, pp. 98–104, 2000. View at Publisher · View at Google Scholar · View at Scopus
  77. J. L. Sullivan, “Iron and sex difference in heart disease risk,” The Lancet, vol. 317, no. 8233, pp. 1293–1294, 1981. View at Publisher · View at Google Scholar · View at Scopus
  78. J. L. Sullivan, “Stored iron and ischemic heart disease: empirical support for a new paradigm,” Circulation, vol. 86, no. 3, pp. 1036–1037, 1992. View at Publisher · View at Google Scholar · View at Scopus
  79. D. A. Patel, S. R. Srinivasan, J.-H. Xu, W. Chen, and G. S. Berenson, “Persistent elevation of liver function enzymes within the reference range is associated with increased cardiovascular risk in young adults: the Bogalusa Heart Study,” Metabolism: Clinical and Experimental, vol. 56, no. 6, pp. 792–798, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. K. E. Brown, M. T. Kinter, T. D. Oberley et al., “Enhanced γ-glutamyl transpeptidase expression and selective loss of CuZn superoxide dismutase in hepatic iron overload,” Free Radical Biology and Medicine, vol. 24, no. 4, pp. 545–555, 1998. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Paolicchi, S. Dominici, L. Pieri, E. Maellaro, and A. Pompella, “Glutathione catabolism as a signaling mechanism,” Biochemical Pharmacology, vol. 64, no. 5, pp. 1027–1035, 2002. View at Publisher · View at Google Scholar · View at Scopus
  82. V. M. Moyo, E. Mvundura, H. Khumalo et al., “Serum ferritin concentrations in Africans with low dietary iron,” Annals of Hematology, vol. 88, no. 11, pp. 1131–1136, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. R. W. Lambrecht, R. K. Sterling, D. Naishadham et al., “Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C,” Gastroenterology, vol. 140, no. 5, pp. 1490–1500, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. H. L. Bonkovsky, D. Naishadham, R. W. Lambrecht et al., “Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C,” Gastroenterology, vol. 131, no. 5, pp. 1440–1451, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. J. E. Everhart and E. C. Wright, “Association of γ-glutamyl transferase (GGT) activity with treatment and clinical outcomes in chronic hepatitis C (HCV),” Hepatology, vol. 57, no. 5, pp. 1725–1733, 2013. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Lemoine, Y. Shimakawa, S. Nayagam et al., “The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa,” Gut, 2015. View at Publisher · View at Google Scholar
  87. World Health Organization, Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection, WHO, 2015, http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf?ua=1&ua=1.
  88. A. T. Eminler, K. Irak, T. Ayyildiz et al., “The relation between liver histopathology and GGT levels in viral hepatitis: more important in hepatitis B,” The Turkish Journal of Gastroenterology, vol. 25, no. 4, pp. 411–415, 2014. View at Publisher · View at Google Scholar · View at Scopus
  89. R. P. Myers, M.-H. Tainturier, V. Ratziu et al., “Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B,” Journal of Hepatology, vol. 39, no. 2, pp. 222–230, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. R. T. Acton, J. C. Barton, L. V. Passmore et al., “Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the Hemochromatosis and Iron Overload Screening (HEIRS) study,” Diabetes Care, vol. 29, no. 9, pp. 2084–2089, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. M. E. Olesnevich, M. F. Kuczmarski, M. Mason, C. Fang, A. B. Zonderman, and M. K. Evans, “Serum ferritin levels associated with increased risk for developing CHD in a low-income urban population,” Public Health Nutrition, vol. 15, no. 7, pp. 1291–1298, 2012. View at Publisher · View at Google Scholar · View at Scopus
  92. M. E. Olesnevich, M. F. Kuczmarski, M. Mason, C. Fang, A. B. Zonderman, and M. K. Evans, “Serum ferritin levels associated with increased risk for developing CHD in a low-income urban population-corrigendum,” Public Health Nutrition, vol. 15, no. 6, article 1138, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. Y. Zhan, Z. Tang, and J. Yu, “Serum ferritin, diabetes, diabetes control, and insulin resistance,” Acta Diabetologica, vol. 51, no. 6, pp. 991–998, 2014. View at Publisher · View at Google Scholar · View at Scopus
  94. L. Sun, O. H. Franco, F. B. Hu et al., “Ferritin concentrations, metabolic syndrome, and type 2 diabetes in middle-aged and elderly Chinese,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 12, pp. 4690–4696, 2008. View at Publisher · View at Google Scholar · View at Scopus
  95. WHO, Serum Ferritin Concentrations for the Assessment of Iron Status and Iron Deficiency in Populations. Vitamin and Mineral Nutrition Information System, WHO/NMH/NHD/MNM/11.2, World Health Organization, Geneva, Switzerland, 2011, http://www.who.int/vmnis/indicators/serum_ferritin.pdf.
  96. S. Ryu, Y. Chang, D.-I. Kim, W. S. Kim, and B.-S. Suh, “γ-glutamyltransferase as a predictor of chronic kidney disease in nonhypertensive and nondiabetic Korean men,” Clinical Chemistry, vol. 53, no. 1, pp. 71–77, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. D.-H. Lee, M.-H. Ha, S. Kam et al., “A strong secular trend in serum gamma-glutamyltransferase from 1996 to 2003 among South Korean men,” American Journal of Epidemiology, vol. 163, no. 1, pp. 57–65, 2006. View at Publisher · View at Google Scholar · View at Scopus
  98. W.-Y. Park, S.-H. Kim, Y. O. Kim et al., “Serum gamma-glutamyltransferase levels predict mortality in patients with peritoneal dialysis,” Medicine, vol. 94, no. 31, Article ID e1249, 2015. View at Publisher · View at Google Scholar
  99. K. Sun, F. Li, D. Lin et al., “Serum gamma—glutamyltransferase is associated with albuminuria: a population-based study,” PLoS ONE, vol. 9, no. 12, Article ID e114970, 2014. View at Publisher · View at Google Scholar · View at Scopus
  100. I. J. Perry, S. G. Wannamethee, and A. G. Shaper, “Prospective study of serum γ-glutamyltransferase and risk of NIDDM,” Diabetes Care, vol. 21, no. 5, pp. 732–737, 1998. View at Publisher · View at Google Scholar · View at Scopus
  101. A. Gautier, B. Balkau, C. Lange, J. Tichet, and F. Bonnet, “Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of γ-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR),” Diabetologia, vol. 53, no. 2, pp. 247–253, 2010. View at Publisher · View at Google Scholar
  102. S. Teppala, A. Shankar, J. Li, T. Y. Wong, and A. Ducatman, “Association between serum γ-glutamyltransferase and chronic kidney disease among us adults,” Kidney and Blood Pressure Research, vol. 33, no. 1, pp. 1–6, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. Y. Wang and M. A. Beydoun, “The obesity epidemic in the United States—gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis,” Epidemiologic Reviews, vol. 29, no. 1, pp. 6–28, 2007. View at Publisher · View at Google Scholar · View at Scopus