Title |
HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype‐stratified cohort study of hemochromatosis in Australian women
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Published in |
Journal of Gastroenterology & Hepatology, March 2017
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DOI | 10.1111/jgh.13621 |
Pubmed ID | |
Authors |
Charles D Warne, Sophie G Zaloumis, Nadine A Bertalli, Martin B Delatycki, Amanda J Nicoll, Christine E McLaren, John L Hopper, Graham G Giles, Greg J Anderson, John K Olynyk, Lawrie W Powell, Katrina J Allen, Lyle C Gurrin, for the HealthIron Study Investigators |
Abstract |
Women who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably due to the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p.C282Y nor p.H63D mutations (HFE wild-types) as comparison groups. A sample of the Melbourne Collaborative Cohort Study (MCCS) was selected for the "HealthIron" study (n = 1,438) including all HFE p.C282Y homozygotes plus a random sample stratified by HFE-genotype (p.C282Y and p.H63D). The relationship between the natural logarithm of SF and time since menopause was examined using linear mixed models incorporating spline smoothing. For p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), p < 0.001) during the first ten years post menopause, after which SF continued to increase but at less than half the previous rate. In contrast, SF profiles for other HFE genotype groups increase more gradually and did not show a distinction between pre- and post-menopausal SF levels. Only p.C282Y homozygotes had predicted SF exceeding 200 µg/L post-menopause, but the projected SF did not increase the risk of iron-overload related disease. These data provide the first documented evidence that physiological blood loss is a major factor in determining the marked gender difference in expression of p.C282Y homozygosity. This article is protected by copyright. All rights reserved. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 50% |
Australia | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 27 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 5 | 19% |
Student > Bachelor | 4 | 15% |
Student > Doctoral Student | 2 | 7% |
Professor | 2 | 7% |
Other | 1 | 4% |
Other | 4 | 15% |
Unknown | 9 | 33% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 9 | 33% |
Nursing and Health Professions | 2 | 7% |
Agricultural and Biological Sciences | 2 | 7% |
Social Sciences | 1 | 4% |
Mathematics | 1 | 4% |
Other | 0 | 0% |
Unknown | 12 | 44% |