Iron-overload-related disease in HFE hereditary hemochromatosis

Allen, Katrina J., Gurrin, Lyle C., Constantine, Clare C., Osborne, Nicholas J., Delatycki, Martin B., Nicoll, Amanda J., McLaren, Christine E., Bahlo, Melanie, Nisselle, Amy E., Vulpe, Chris D., Anderson, Gregory J., Southey, Melissa C., Giles, Graham G., English, Dallas R., Hopper, John L., Olynyk, John K., Powell, Lawrie W. and Gertig, Dorota M. (2008) Iron-overload-related disease in HFE hereditary hemochromatosis. New England Journal of Medicine, 358 3: 221-230. doi:10.1056/NEJMoa073286

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Author Allen, Katrina J.
Gurrin, Lyle C.
Constantine, Clare C.
Osborne, Nicholas J.
Delatycki, Martin B.
Nicoll, Amanda J.
McLaren, Christine E.
Bahlo, Melanie
Nisselle, Amy E.
Vulpe, Chris D.
Anderson, Gregory J.
Southey, Melissa C.
Giles, Graham G.
English, Dallas R.
Hopper, John L.
Olynyk, John K.
Powell, Lawrie W.
Gertig, Dorota M.
Title Iron-overload-related disease in HFE hereditary hemochromatosis
Formatted title
Iron-overload-related disease in HFE hereditary hemochromatosis
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
Publication date 2008-01-17
Sub-type Article (original research)
DOI 10.1056/NEJMoa073286
Open Access Status File (Publisher version)
Volume 358
Issue 3
Start page 221
End page 230
Total pages 10
Place of publication Waltham, MA, United States
Publisher Massachusetts Medical Society
Language eng
Formatted abstract
Background: Most persons who are homozygous for C282Y, the HFE allele most commonly asssociated with hereditary hemochromatosis, have elevated levels of serum ferritin and transferrin saturation. Diseases related to iron overload develop in some C282Y homozygotes, but the extent of the risk is controversial.

Methods: We assessed HFE mutations in 31,192 persons of northern European descent between the ages of 40 and 69 years who participated in the Melbourne Collaborative Cohort Study and were followed for an average of 12 years. In a random sample of 1438 subjects stratified according to HFE genotype, including all 203 C282Y homozygotes (of whom 108 were women and 95 were men), we obtained clinical and biochemical data, including two sets of iron measurements performed 12 years apart. Disease related to iron overload was defined as documented iron overload and one or more of the following conditions: cirrhosis, liver fibrosis, hepatocellular carcinoma, elevated aminotransferase levels, physician-diagnosed symptomatic hemochromatosis, and arthropathy of the second and third metacarpophalangeal joints.

Results: The proportion of C282Y homozygotes with documented iron-overload–related disease was 28.4% (95% confidence interval [CI], 18.8 to 40.2) for men and 1.2% (95% CI, 0.03 to 6.5) for women. Only one non-C282Y homozygote (a compound heterozygote) had documented iron-overload–related disease. Male C282Y homozygotes with a serum ferritin level of 1000 μg per liter or more were more likely to report fatigue, use of arthritis medicine, and a history of liver disease than were men who had the wild-type gene.

Conclusions: In persons who are homozygous for the C282Y mutation, iron-overload–related disease developed in a substantial proportion of men but in a small proportion of women.
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Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 329 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 20:37:37 EST by Mr Andrew Martlew on behalf of School of Medicine