HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity

Gurrin, Lyle C., Bertalli, Nadine A., Dalton, Gregory W., Osborne, Nicholas J., Constantine, Clare C., McLaren, Christine E., English, Dallas R., Gertig, Dorota M., Delatycki, Martin B., Nicoll, Amanda J., Southey, Melissa C., Hopper, John L., Giles, Graham G., Anderson, Gregory J., Olunyk, John K., Powell, Lawrie W. and Allen, Katrina J. (2009) HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity. Hepatology, 50 1: 94-101. doi:10.1002/hep.22972

Author Gurrin, Lyle C.
Bertalli, Nadine A.
Dalton, Gregory W.
Osborne, Nicholas J.
Constantine, Clare C.
McLaren, Christine E.
English, Dallas R.
Gertig, Dorota M.
Delatycki, Martin B.
Nicoll, Amanda J.
Southey, Melissa C.
Hopper, John L.
Giles, Graham G.
Anderson, Gregory J.
Olunyk, John K.
Powell, Lawrie W.
Allen, Katrina J.
Title HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity
Formatted title
HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity
Journal name Hepatology   Check publisher's open access policy
ISSN 0270-9139
Publication date 2009-07-01
Sub-type Article (original research)
DOI 10.1002/hep.22972
Open Access Status DOI
Volume 50
Issue 1
Start page 94
End page 101
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were premenopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 μg/L for compound heterozygotes and from 35 to 64 μg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease. Conclusion: For male compound heterozygotes, mean iron indices do not change during middle age but for female compound heterozygotes menopause results in increased mean SF. Although compound heterozygotes might maintain elevated iron indices during middle age, documented iron overload-related disease is rare.
Q-Index Code C1
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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Created: Thu, 03 Sep 2009, 17:53:42 EST by Mr Andrew Martlew on behalf of School of Medicine