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Title: HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: a genotype-stratified cohort study of hemochromatosis in Australian women
Authors: Warne, Charles D;Zaloumis, Sophie G;Bertalli, Nadine A;Delatycki, Martin B;Nicoll, Amanda J;McLaren, Christine E;Hopper, John L;Giles, Graham G;Anderson, Gregory J;Olynyk, John K;Powell, Lawrie W;Allen, Katrina J;Gurrin, Lyle C;The HealthIron Study Investigators
Issue Date: Apr-2017
Citation: Journal of Gastroenterology and Hepatology 2017; 32(4): 797-802
Abstract: BACKGROUND AND AIM: 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 because of 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. METHODS: A sample of the Melbourne Collaborative Cohort Study was selected for the "HealthIron" study (n = 1438) 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. RESULTS: For p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), P < 0.001) during the first 10 years postmenopause, 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 premenopausal and postmenopausal SF levels. Only p.C282Y homozygotes had predicted SF exceeding 200 μg/L postmenopause, but the projected SF did not increase the risk of iron overload-related disease. CONCLUSIONS: 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.
DOI: 10.1111/jgh.13621
PubMed URL:
Type: Journal Article
Subjects: HFE p.C282Y homozygosity
Hereditary hemochromatosis
Iron accumulation
Iron overload-related disease
Women's health
Appears in Collections:Journal articles

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