Gastroenterology
Volume 135, Issue 6 , Pages 1945-1952 , December 2008

The Natural History of Serum Iron Indices for HFE C282Y Homozygosity Associated With Hereditary Hemochromatosis

  • Lyle C. Gurrin

      Affiliations

    • Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
    • ,
  • Nicholas J. Osborne

      Affiliations

    • Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
    • Murdoch Childrens Research Institute, Victoria, Australia
    • ,
  • Clare C. Constantine

      Affiliations

    • Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
    • Department of Epidemiology University of California, Irvine, California
    • ,
  • Christine E. McLaren

      Affiliations

    • Department of Epidemiology University of California, Irvine, California
    • ,
  • Dallas R. English

      Affiliations

    • Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
    • Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia
    • ,
  • Dorota M. Gertig

      Affiliations

    • Victorian Cervical Cytology Registry, Melbourne, Australia
    • ,
  • Martin B. Delatycki

      Affiliations

    • Murdoch Childrens Research Institute, Victoria, Australia
    • Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Victoria, Australia
    • ,
  • Melissa C. Southey

      Affiliations

    • Department of Pathology, The University of Melbourne, Melbourne, Australia
    • ,
  • John L. Hopper

      Affiliations

    • Centre for MEGA Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Australia
    • ,
  • Graham G. Giles

      Affiliations

    • Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia
    • ,
  • Gregory J. Anderson

      Affiliations

    • Queensland Institute of Medical Research and the University of Queensland, Brisbane, Australia
    • ,
  • John K. Olynyk

      Affiliations

    • Department of Gastroenterology, Fremantle Hospital, Fremantle, Australia
    • School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia
    • Western Australian Institute of Medical Research, Perth, Australia
    • ,
  • Laurie W. Powell

      Affiliations

    • Queensland Institute of Medical Research and the University of Queensland, Brisbane, Australia
    • The University of Queensland and the Royal Brisbane and Women's Hospital, Brisbane, Australia
    • ,
  • Katrina J. Allen

      Affiliations

    • Murdoch Childrens Research Institute, Victoria, Australia
    • Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Victoria, Australia
    • Department of Gastroenterology, Royal Children's Hospital, Victoria, Australia
    • Corresponding Author InformationAddress requests for reprints to: Katie Allen, Associate Professor, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Rd, Parkville, 3025, Victoria, Australia. fax: (61) 3 9345 6240
    • ,
  • HealthIron Study Investigators

Received 25 April 2008 ,Accepted 28 August 2008.

References 

  1. Koziol JA, Ho NJ, Felitti VJ, et al. Reference centiles for serum ferritin and percentage of transferrin saturation, with application to mutations of the HFE gene. Clin Chem. 2001;47:1804–1810
  2. Allen KJ, Gurrin LC, Constantine CC, et al. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med. 2008;358:221–230
  3. Powell LW. Hemochromatosis: the impact of early diagnosis and therapy. Gastroenterology. 1996;110:1304–1307
  4. Cook JD, Skikne BS, Lynch SR, et al. Estimates of iron sufficiency in the US population. Blood. 1986;68:726–731
  5. Morrison ED, Brandhagen DJ, Phatak PD, et al. Serum ferritin level predicts advanced hepatic fibrosis among US patients with phenotypic hemochromatosis. Ann Intern Med. 2003;138:627–633
  6. Powell LW, Dixon JL, Ramm GA, et al. Screening for hemochromatosis in asymptomatic subjects with or without a family history. Arch Intern Med. 2006;166:294–301
  7. Guyader D, Jacquelinet C, Moirand R, et al. Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. Gastroenterology. 1998;115:929–936
  8. Adams PC. Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis?. Am J Gastroenterol. 2001;96:567–569
  9. Bassett ML, Halliday JW, Powell LW. Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology. 1986;6:24–29
  10. Beaton MD, Adams PC. Prognostic factors and survival in patients with hereditary hemochromatosis and cirrhosis. Can J Gastroenterol. 2006;20:257–260
  11. Tavill AS. Diagnosis and management of hemochromatosis. Hepatology. 2001;33:1321–1328
  12. Adams P, Brissot P, Powell LW. EASL International Consensus Conference on Haemochromatosis. J Hepatol. 2000;33:485–504
  13. Bacon BR. Hemochromatosis: diagnosis and management. Gastroenterology. 2001;120:718–725
  14. Allen KJ, Nisselle AE, Collins VR, et al. Asymptomatic individuals at genetic risk of haemochromatosis take appropriate steps to prevent disease related to iron overload. Liver International. 2008;28:363–369
  15. Andersen RV, Tybjaerg-Hansen A, Appleyard M, et al. Hemochromatosis mutations in the general population: iron overload progression rate. Blood. 2004;103:2914–2919
  16. Olynyk JK, Hagan SE, Cullen DJ, et al. Evolution of untreated hereditary hemochromatosis in the Busselton population: a 17-year study. Mayo Clin Proc. 2004;79:309–313
  17. Giles GG, English DR. The Melbourne Collaborative Cohort Study. IARC Sci Publ. 2002;156:69–70
  18. Whitfield JB, Treloar S, Zhu G, et al. Relative importance of female-specific and non-female specific effects on variation in iron stores between women. Br J Haemotol. 2003;120:860–866
  19. Whitlock EP, Garlitz BA, Harris EL, et al. Screening for hereditary hemochromatosis: a systematic review for the US Preventive Services Task Force. Ann Intern Med. 2006;145:209–223
  20. Gelman A, Carlin JB, Stern H. Bayesian data analysis. Chapman and Hall; 2003;
  21. Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med. 2005;352:1769–1778
  22. Delatycki MB, Allen KJ, Nisselle AE, et al. Use of community genetic screening to prevent HFE-associated hereditary haemochromatosis. Lancet. 2005;366:314–316
  23. Beutler E, Felitti VJ, Koziol JA, et al. Penetrance of 845G>A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet. 2002;359:211–218
  24. Asberg A, Hveem K, Thorstensen K, et al. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol. 2001;36:1108–1115
  25. Olynyk JK, Cullen DJ, Aquilia S, et al. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med. 1999;341:718–724
  26. Deugnier Y, Jouanolle AM, Chaperon J, et al. Gender-specific phenotypic expression and screening strategies in C282Y-linked haemochromatosis: a study of 9396 French people. Br J Haematol. 2002;118:1170–1178
  27. Waalen J, Beutler E. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med. 2008;358:2293–2295
  28. Yamashita C, Adams PC. Natural history of the C282Y homozygote for the hemochromatosis gene (HFE) with a normal serum ferritin level. Clin Gastroenterol Hepatol. 2003;1:388–391
  29. McLaren GD, Nathanson MH, Jacobs A, et al. Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis. J Lab Clin Med. 1991;117:390–401
  30. Barton JC, Preston BL, McDonnell SM, et al. Severity of iron overload in hemochromatosis: effect of volunteer blood donation before diagnosis. Transfusion. 2001;41:123–129

 The HealthIron Study Investigators also include Melanie Bahlo (The Walter & Eliza Hall Institute for Medical Research, Melbourne, Australia), Amanda Nicoll (Royal Melbourne Hospital, Melbourne, Australia), Amy Nisselle (Murdoch Childrens Research Institute, Melbourne, Australia), and Chris Vulpe (University of California, Berkeley, California).

 The authors disclose the following: Supported by the National Institute of Diabetes, Digestive and Kidney Diseases (US) (1 RO1 DK061885-01 A2); National Health and Medical Research Council (NHMRC) (Australia) (project grant number 251668); by VicHealth and The Cancer Council Victoria for cohort recruitment; The Cancer Council Victoria and the NHMRC (program grant 209057, enabling grant 396414) for continuing follow-up; and by NHMRC Career Development Award (to L.C.G. and K.J.A), NHMRC Practitioner Fellowship (to M.B.D. and J.K.O), NHMRC Senior Research Fellowship (to M.C.S and G.J.A.), and NHMRC Australia Fellowship (to J.L.H.).

PII: S0016-5085(08)01666-1

doi: 10.1053/j.gastro.2008.08.056

Gastroenterology
Volume 135, Issue 6 , Pages 1945-1952 , December 2008

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