HFE Cys282Tyr Homozygotes With Serum Ferritin Concentrations Below 1000 mu g/L Are at Low Risk of Hemochromatosis

Allen, Katrina J., Bertalli, Nadine A., Osborne, Nicholas J., Constantine, Clare C., Delatycki, Martin B., Nisselle, Amy E., Nicoll, Amanda J., Gertig, Dorota M., McLaren, Christine E., Giles, Graham G., Hopper, John L., Anderson, Gregory J., Olynyk, John K., Powell, Lawrie W., Gurrin, Lyle C. and HealthIron Study Investigators (2010) HFE Cys282Tyr Homozygotes With Serum Ferritin Concentrations Below 1000 mu g/L Are at Low Risk of Hemochromatosis. Hepatology, 52 3: 925-933. doi:10.1002/hep.23786

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Author Allen, Katrina J.
Bertalli, Nadine A.
Osborne, Nicholas J.
Constantine, Clare C.
Delatycki, Martin B.
Nisselle, Amy E.
Nicoll, Amanda J.
Gertig, Dorota M.
McLaren, Christine E.
Giles, Graham G.
Hopper, John L.
Anderson, Gregory J.
Olynyk, John K.
Powell, Lawrie W.
Gurrin, Lyle C.
HealthIron Study Investigators
Title HFE Cys282Tyr Homozygotes With Serum Ferritin Concentrations Below 1000 mu g/L Are at Low Risk of Hemochromatosis
Formatted title
HFE Cys282Tyr homozygotes with serum ferritin concentrations below 1000 μg/L are at low risk of hemochromatosis
Journal name Hepatology   Check publisher's open access policy
ISSN 0270-9139
Publication date 2010-09
Sub-type Article (original research)
DOI 10.1002/hep.23786
Volume 52
Issue 3
Start page 925
End page 933
Total pages 9
Editor Keith D. Lindor
Place of publication Hoboken, NJ, U.S.A.
Publisher Wiley Interscience
Collection year 2011
Language eng
Formatted abstract
Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost 1 million persons in the United States. Most clinical cases are homozygous for the Cys282Tyr (C282Y) mutation in the HFE gene, with serum ferritin (SF) concentration >1000 μg/L as the strongest predictor of cirrhosis. The optimal treatment regimen for those with SF concentrations above the normal range but <1000 μg/L is unknown. We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants' HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131 male, 160 female) with baseline and follow-up SF concentrations <1000 μg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and HFE wild-types for both normal and moderately elevated SF concentrations. The maximum prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval = −6%, 29%; P = 0.22) and for normal SF was 6% (arthritis medicine use, 95% confidence interval = −3%, 16%; P = 0.11). Conclusion: Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 μg/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C282Y homozygotes.
Copyright © 2010 by the American Association for the Study of Liver Diseases
Keyword Hereditary hemochromatosis
H63D mutations
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published under "Steatohepatitis/Metabolic Liver Disease".

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 20 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 19 Sep 2010, 00:06:25 EST